Pub Date : 2024-10-16DOI: 10.1007/s00335-024-10078-9
Jian Zhang, Huiwen Wang, Qianbing Wang, Juan Mo, Lei Fu, Shifang Peng
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease that ranges from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), and may eventually progress to cirrhosis and hepatocellular carcinoma (HCC). The underlying mechanism of MASLD remains incompletely understood. This study aimed to identify key gene implicated in MASLD pathogenesis and validate its correlation with disease severity through an integration of bioinformatics and experimental approaches. Liver transcriptome data from MASLD patients were obtained from the Gene Expression Omnibus (GEO) database. A diet-induced MASLD mouse model was developed, and liver RNA-sequencing was performed. Liver specimens and clinical data from patients were collected for further analysis. A total of 120 differentially expressed genes (DEGs) were shared between datasets GSE89632 and GSE213621, with functional enrichment in inflammatory, metabolic, and cell cycle-related pathways. Protein-protein interaction (PPI) network analysis identified three modules associated with MASLD, with the cell cycle-related module being the most notable. EEF1A2 was identified as a novel hub gene and revealed to be elevated with MASLD progression through dataset analysis. EEF1A2 was confirmed to be highly expressed in the livers of both MASLD mouse models and patients. Moreover, the increased expression of EEF1A2 in MASH was positively correlated with higher serum alanine aminotransferase (ALT), alanine aminotransferase (AST), total cholesterol (TC), and body mass index (BMI). In conclusion, EEF1A2 is a novel hub gene significantly associated with MASLD severity and is a promising biomarker and therapeutic target for MASLD.
{"title":"EEF1A2 identified as a hub gene associated with the severity of metabolic dysfunction-associated steatotic liver disease.","authors":"Jian Zhang, Huiwen Wang, Qianbing Wang, Juan Mo, Lei Fu, Shifang Peng","doi":"10.1007/s00335-024-10078-9","DOIUrl":"https://doi.org/10.1007/s00335-024-10078-9","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease that ranges from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), and may eventually progress to cirrhosis and hepatocellular carcinoma (HCC). The underlying mechanism of MASLD remains incompletely understood. This study aimed to identify key gene implicated in MASLD pathogenesis and validate its correlation with disease severity through an integration of bioinformatics and experimental approaches. Liver transcriptome data from MASLD patients were obtained from the Gene Expression Omnibus (GEO) database. A diet-induced MASLD mouse model was developed, and liver RNA-sequencing was performed. Liver specimens and clinical data from patients were collected for further analysis. A total of 120 differentially expressed genes (DEGs) were shared between datasets GSE89632 and GSE213621, with functional enrichment in inflammatory, metabolic, and cell cycle-related pathways. Protein-protein interaction (PPI) network analysis identified three modules associated with MASLD, with the cell cycle-related module being the most notable. EEF1A2 was identified as a novel hub gene and revealed to be elevated with MASLD progression through dataset analysis. EEF1A2 was confirmed to be highly expressed in the livers of both MASLD mouse models and patients. Moreover, the increased expression of EEF1A2 in MASH was positively correlated with higher serum alanine aminotransferase (ALT), alanine aminotransferase (AST), total cholesterol (TC), and body mass index (BMI). In conclusion, EEF1A2 is a novel hub gene significantly associated with MASLD severity and is a promising biomarker and therapeutic target for MASLD.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1007/s00335-024-10076-x
Robert P Erickson
The T/t complex of the mouse attracted many of the major figures of mouse genetics to perform genetic, cytogenetic, physiological, biochemical and molecular biological studies of it. These studies started with the discovery of short tailed mutants (Ts) and recessive lethal developmental mutations (ts) which mapped to the same "locus" in the early 1920s in France. However, due to the non-receptivity of French scientists to genetics, they continued to be studied in mostly Anglophone countries to be joined by a wider international community in the 1970s. These discoveries led to developmental studies of the lethal mutants which provided the origin of mammalian developmental genetics. The fascinating property of transmission ratio distortion (non-50/50 segregation of alleles in offspring of males) elicited tremendous interest. There were false leads (that the region consisted of unusual DNA, that the alleles controlled cell surface antigens on embryonic cells and spermatozoa) and exciting discoveries. This historical review provides a review of this extensive area of research and some of the individuals involved in it.
{"title":"A fascination with tailless mice: a scientific historical review of studies of the T/t complex.","authors":"Robert P Erickson","doi":"10.1007/s00335-024-10076-x","DOIUrl":"https://doi.org/10.1007/s00335-024-10076-x","url":null,"abstract":"<p><p>The T/t complex of the mouse attracted many of the major figures of mouse genetics to perform genetic, cytogenetic, physiological, biochemical and molecular biological studies of it. These studies started with the discovery of short tailed mutants (Ts) and recessive lethal developmental mutations (ts) which mapped to the same \"locus\" in the early 1920s in France. However, due to the non-receptivity of French scientists to genetics, they continued to be studied in mostly Anglophone countries to be joined by a wider international community in the 1970s. These discoveries led to developmental studies of the lethal mutants which provided the origin of mammalian developmental genetics. The fascinating property of transmission ratio distortion (non-50/50 segregation of alleles in offspring of males) elicited tremendous interest. There were false leads (that the region consisted of unusual DNA, that the alleles controlled cell surface antigens on embryonic cells and spermatozoa) and exciting discoveries. This historical review provides a review of this extensive area of research and some of the individuals involved in it.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Livestock plays an essential role in sustaining human livelihoods, offering a diverse range of species integral to food security, economic stability, and cultural traditions. The domestication of livestock, which began over 10,000 years ago, has driven significant genetic changes in species such as cattle, buffaloes, sheep, goats, and pigs. Recent advancements in genomic technologies, including next-generation sequencing (NGS), genome-wide association studies (GWAS), and genomic selection, have dramatically enhanced our understanding of these genetic developments. This review brings together key research on the domestication process, phylogenetics, genetic diversity, and selection signatures within major livestock species. It emphasizes the importance of admixture studies and evolutionary forces like natural selection, genetic drift, and gene flow in shaping livestock populations. Additionally, the integration of machine learning with genomic data offers new perspectives on the functional roles of genes in adaptation and evolution. By exploring these genomic advancements, this review provides insights into genetic variation and evolutionary processes that could inform future approaches to improving livestock management and adaptation to environmental challenges, including climate change.
{"title":"A comprehensive review of livestock development: insights into domestication, phylogenetics, diversity, and genomic advances.","authors":"Sonali Sonejita Nayak, Divya Rajawat, Karan Jain, Anurodh Sharma, Cedric Gondro, Ayon Tarafdar, Triveni Dutt, Manjit Panigrahi","doi":"10.1007/s00335-024-10075-y","DOIUrl":"https://doi.org/10.1007/s00335-024-10075-y","url":null,"abstract":"<p><p>Livestock plays an essential role in sustaining human livelihoods, offering a diverse range of species integral to food security, economic stability, and cultural traditions. The domestication of livestock, which began over 10,000 years ago, has driven significant genetic changes in species such as cattle, buffaloes, sheep, goats, and pigs. Recent advancements in genomic technologies, including next-generation sequencing (NGS), genome-wide association studies (GWAS), and genomic selection, have dramatically enhanced our understanding of these genetic developments. This review brings together key research on the domestication process, phylogenetics, genetic diversity, and selection signatures within major livestock species. It emphasizes the importance of admixture studies and evolutionary forces like natural selection, genetic drift, and gene flow in shaping livestock populations. Additionally, the integration of machine learning with genomic data offers new perspectives on the functional roles of genes in adaptation and evolution. By exploring these genomic advancements, this review provides insights into genetic variation and evolutionary processes that could inform future approaches to improving livestock management and adaptation to environmental challenges, including climate change.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1007/s00335-024-10077-w
Xi Yong, Tengyao Kang, Mingzhu Li, Sixuan Li, Xiang Yan, Jiuxin Li, Jie Lin, Bo Lu, Jianghua Zheng, Zhengmin Xu, Qin Yang, Jingdong Li
Atherosclerosis (AS) is a predominant etiological factor in numerous cardiovascular diseases, with its associated complications such as myocardial infarction and stroke serving as major contributors to worldwide mortality rates. Here, we devised dependable AS-related biomarkers through the utilization of single-cell RNA sequencing, weighted co-expression network (WGCNA), and differential expression analysis. Furthermore, we employed various machine learning techniques (LASSO and SVM-RFE) to enhance the identification of AS biomarkers, subsequently validating them using the GEO dataset. Following this, CIBERSORT was employed to investigate the correlation between biomarkers and infiltrating immune cells. Consequently, 256 differentially expressed genes (DEGs) were selected in samples of AS and normal. GO and KEGG analyses indicated that these DEGs may be related to the negative regulation of leukocyte-mediated immunity, leukocyte cell-cell adhesion, and immune system processes. Notably, C1QC and COL1A1 were pinpointed as potential diagnostic markers for AS, a finding that was further validated in the GSE21545 dataset. Moreover, the area under the curve (AUC) values for these markers exceeded 0.8, underscoring their diagnostic utility. Analysis of immune cell infiltration revealed that the expression of C1QC was correlated with M0 macrophages, gamma delta T cells, activated mast cells and memory B cells. Similarly, COL1A1 expression was linked to M0 macrophages, memory B cells, activated mast cells, gamma delta T cells, and CD4 native T cells. Finally, these results were validated using mice and human samples through immunofluorescence, immunohistochemistry, and ELISA analysis. Overall, C1QC and COL1A1 would be potential biomarkers for AS diagnosis, and that would provides novel perspectives on the diagnosis and treatment of AS.
动脉粥样硬化(AS)是多种心血管疾病的主要致病因素,其相关并发症如心肌梗死和中风是造成全球死亡率的主要原因。在这里,我们利用单细胞 RNA 测序、加权共表达网络(WGCNA)和差异表达分析,设计出了可靠的 AS 相关生物标志物。此外,我们还采用了多种机器学习技术(LASSO 和 SVM-RFE)来提高强直性脊柱炎生物标志物的识别能力,并随后利用 GEO 数据集对其进行了验证。随后,我们使用 CIBERSORT 研究了生物标志物与浸润免疫细胞之间的相关性。结果,在强直性脊柱炎样本和正常样本中筛选出了 256 个差异表达基因(DEG)。GO和KEGG分析表明,这些DEGs可能与白细胞介导的免疫、白细胞细胞间粘附和免疫系统过程的负调控有关。值得注意的是,C1QC和COL1A1被认为是强直性脊柱炎的潜在诊断标志物,这一发现在GSE21545数据集中得到了进一步验证。此外,这些标记物的曲线下面积(AUC)值超过了0.8,突显了它们的诊断效用。对免疫细胞浸润的分析表明,C1QC 的表达与 M0 巨噬细胞、γ delta T 细胞、活化肥大细胞和记忆 B 细胞相关。同样,COL1A1 的表达与 M0 巨噬细胞、记忆 B 细胞、活化肥大细胞、γ delta T 细胞和 CD4 原生 T 细胞有关。最后,通过免疫荧光、免疫组织化学和酶联免疫吸附分析,使用小鼠和人类样本对这些结果进行了验证。总之,C1QC和COL1A1将成为诊断强直性脊柱炎的潜在生物标志物,为强直性脊柱炎的诊断和治疗提供新的视角。
{"title":"Identification of novel biomarkers for atherosclerosis using single-cell RNA sequencing and machine learning.","authors":"Xi Yong, Tengyao Kang, Mingzhu Li, Sixuan Li, Xiang Yan, Jiuxin Li, Jie Lin, Bo Lu, Jianghua Zheng, Zhengmin Xu, Qin Yang, Jingdong Li","doi":"10.1007/s00335-024-10077-w","DOIUrl":"https://doi.org/10.1007/s00335-024-10077-w","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a predominant etiological factor in numerous cardiovascular diseases, with its associated complications such as myocardial infarction and stroke serving as major contributors to worldwide mortality rates. Here, we devised dependable AS-related biomarkers through the utilization of single-cell RNA sequencing, weighted co-expression network (WGCNA), and differential expression analysis. Furthermore, we employed various machine learning techniques (LASSO and SVM-RFE) to enhance the identification of AS biomarkers, subsequently validating them using the GEO dataset. Following this, CIBERSORT was employed to investigate the correlation between biomarkers and infiltrating immune cells. Consequently, 256 differentially expressed genes (DEGs) were selected in samples of AS and normal. GO and KEGG analyses indicated that these DEGs may be related to the negative regulation of leukocyte-mediated immunity, leukocyte cell-cell adhesion, and immune system processes. Notably, C1QC and COL1A1 were pinpointed as potential diagnostic markers for AS, a finding that was further validated in the GSE21545 dataset. Moreover, the area under the curve (AUC) values for these markers exceeded 0.8, underscoring their diagnostic utility. Analysis of immune cell infiltration revealed that the expression of C1QC was correlated with M0 macrophages, gamma delta T cells, activated mast cells and memory B cells. Similarly, COL1A1 expression was linked to M0 macrophages, memory B cells, activated mast cells, gamma delta T cells, and CD4 native T cells. Finally, these results were validated using mice and human samples through immunofluorescence, immunohistochemistry, and ELISA analysis. Overall, C1QC and COL1A1 would be potential biomarkers for AS diagnosis, and that would provides novel perspectives on the diagnosis and treatment of AS.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1007/s00335-024-10073-0
Dianxia Xing, Wenjin Zhang, Yan Liu, Hong Huang, Junjie Xie
Alzheimer's Disease (AD) remains a significant challenge due to its complex etiology and socio-economic burden. In this study, we investigated the roles of macrophage polarization-related hub genes in AD pathology, focusing on their impact on immune infiltration and gene regulation in distinct brain regions. Using Gene Expression Omnibus (GEO) datasets GSE110226 (choroid plexus) and GSE1297 (hippocampal CA1), we identified key genes-EDN1, HHLA2, KL, TREM2, and WWTR1-associated with AD mechanisms and immune responses. Based on these findings, we developed a diagnostic model demonstrating favorable calibration and clinical applicability. Furthermore, we explored molecular interactions within mRNA-transcription factor and mRNA-miRNA regulatory networks, providing deeper insights into AD progression and identifying potential therapeutic targets. The novel identification of WWTR1 and HHLA2 as biomarkers expands the diagnostic toolkit for AD, offering new perspectives on the disease's underlying immune dynamics. However, external dataset validation and further in vitro and in vivo studies are required to confirm these results and their clinical relevance.
{"title":"Genes related to microglia polarization and immune infiltration in Alzheimer's Disease.","authors":"Dianxia Xing, Wenjin Zhang, Yan Liu, Hong Huang, Junjie Xie","doi":"10.1007/s00335-024-10073-0","DOIUrl":"https://doi.org/10.1007/s00335-024-10073-0","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) remains a significant challenge due to its complex etiology and socio-economic burden. In this study, we investigated the roles of macrophage polarization-related hub genes in AD pathology, focusing on their impact on immune infiltration and gene regulation in distinct brain regions. Using Gene Expression Omnibus (GEO) datasets GSE110226 (choroid plexus) and GSE1297 (hippocampal CA1), we identified key genes-EDN1, HHLA2, KL, TREM2, and WWTR1-associated with AD mechanisms and immune responses. Based on these findings, we developed a diagnostic model demonstrating favorable calibration and clinical applicability. Furthermore, we explored molecular interactions within mRNA-transcription factor and mRNA-miRNA regulatory networks, providing deeper insights into AD progression and identifying potential therapeutic targets. The novel identification of WWTR1 and HHLA2 as biomarkers expands the diagnostic toolkit for AD, offering new perspectives on the disease's underlying immune dynamics. However, external dataset validation and further in vitro and in vivo studies are required to confirm these results and their clinical relevance.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The study aimed to investigate prevalent chromosomal breakpoints identified in balanced structural chromosomal anomalies and to pinpoint potential candidate genes linked with male infertility. This was acchieved through a comprehensive approach combining RNA-seq and microarray data analysis, enabling precise identification of candidate genes. The Cytogenetics data from 2,500 infertile males referred to Royan Research Institute between 2009 and 2022 were analyzed, with 391 cases meeting the inclusion criteria of balanced chromosomal rearrangement. Of these, 193 cases exhibited normal variations and were excluded from the analysis. By examining the breakpoints, potential candidate genes were suggested. Among the remaining 198 cases, reciprocal translocations were the most frequent anomaly (129 cases), followed by Robertsonian translocations (43 cases), inversions (34 cases), and insertions (3 cases).Some patients had more than one chromosomal abnormality. Chromosomal anomalies were most frequently observed in chromosomes 13 (21.1%), 14 (20.1%), and 1 (16.3%) with 13q12, 14q12, and 1p36.3 being the most prevalent breakpoints, respectively. Chromosome 1 contributed the most to reciprocal translocations (20.2%) and inversions (17.6%), while chromosome 14 was the most involved in the Robertsonian translocations (82.2%). The findings suggested that breakpoints at 1p36.3 and 14q12 might be associated with pregestational infertility, whereas breakpoints at 13q12 could be linked to both gestational and pregestational infertility. Several candidate genes located on common breakpoints were proposed as potentially involved in male infertility. Bioinformatics analyses utilizing three databases were conducted to examine the expression patterns of 78 candidate genes implicated in various causes of infertility. In azoospermic individuals, significant differential expression was observed in 19 genes: 15 were downregulated (TSSK2, SPINK2, TSSK4, CDY1, CFAP70, BPY2, BTG4, FKBP6, PPP2R1B, SPECC1L, CENPJ, SKA3, FGF9, NODAL, CLOCK), while four genes were upregulated (HSPB1, MIF, PRF1, ENTPD6). In the case of Asthenozoospermia, seven genes showed significant upregulation (PRF1, DDX21, KIT, SRD5A3, MTCH1, DDX50, NODAL). Though RNA-seq data for Teratozoospermia were unavailable, microarray data revealed differential expression insix genes: three downregulated (BUB1, KLK4, PIWIL2) and three upregulated (AURKC, NPM2, RANBP2). These findings enhance our understanding of the molecular basis of male infertility and could provide valuable insights for future diagnostic and therapeutic strategies.
{"title":"Comprehensive analysis of chromosomal breakpoints and candidate genes associated with male infertility: insights from cytogenetic studies and expression analyses.","authors":"Melika Hossein Garakani, Kianoush Kakavand, Marjan Sabbaghian, Azadeh Ghaheri, Najmeh Sadat Masoudi, Maryam Shahhoseini, Vahideh Hassanzadeh, Mohammadreza Zamanian, Anahita Mohseni Meybodi, Shabnam Zarei Moradi","doi":"10.1007/s00335-024-10074-z","DOIUrl":"https://doi.org/10.1007/s00335-024-10074-z","url":null,"abstract":"<p><p>The study aimed to investigate prevalent chromosomal breakpoints identified in balanced structural chromosomal anomalies and to pinpoint potential candidate genes linked with male infertility. This was acchieved through a comprehensive approach combining RNA-seq and microarray data analysis, enabling precise identification of candidate genes. The Cytogenetics data from 2,500 infertile males referred to Royan Research Institute between 2009 and 2022 were analyzed, with 391 cases meeting the inclusion criteria of balanced chromosomal rearrangement. Of these, 193 cases exhibited normal variations and were excluded from the analysis. By examining the breakpoints, potential candidate genes were suggested. Among the remaining 198 cases, reciprocal translocations were the most frequent anomaly (129 cases), followed by Robertsonian translocations (43 cases), inversions (34 cases), and insertions (3 cases).Some patients had more than one chromosomal abnormality. Chromosomal anomalies were most frequently observed in chromosomes 13 (21.1%), 14 (20.1%), and 1 (16.3%) with 13q12, 14q12, and 1p36.3 being the most prevalent breakpoints, respectively. Chromosome 1 contributed the most to reciprocal translocations (20.2%) and inversions (17.6%), while chromosome 14 was the most involved in the Robertsonian translocations (82.2%). The findings suggested that breakpoints at 1p36.3 and 14q12 might be associated with pregestational infertility, whereas breakpoints at 13q12 could be linked to both gestational and pregestational infertility. Several candidate genes located on common breakpoints were proposed as potentially involved in male infertility. Bioinformatics analyses utilizing three databases were conducted to examine the expression patterns of 78 candidate genes implicated in various causes of infertility. In azoospermic individuals, significant differential expression was observed in 19 genes: 15 were downregulated (TSSK2, SPINK2, TSSK4, CDY1, CFAP70, BPY2, BTG4, FKBP6, PPP2R1B, SPECC1L, CENPJ, SKA3, FGF9, NODAL, CLOCK), while four genes were upregulated (HSPB1, MIF, PRF1, ENTPD6). In the case of Asthenozoospermia, seven genes showed significant upregulation (PRF1, DDX21, KIT, SRD5A3, MTCH1, DDX50, NODAL). Though RNA-seq data for Teratozoospermia were unavailable, microarray data revealed differential expression insix genes: three downregulated (BUB1, KLK4, PIWIL2) and three upregulated (AURKC, NPM2, RANBP2). These findings enhance our understanding of the molecular basis of male infertility and could provide valuable insights for future diagnostic and therapeutic strategies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1007/s00335-024-10071-2
Prerna Nair, Karen P Steel, Morag A Lewis
Targeted mouse mutants are a common tool used to investigate gene function. The International Knockout Mouse Consortium undertook a large-scale screen of mouse mutants, making use of the knockout-first allele design that contains the En2 splice acceptor sequence coupled to the lacZ reporter gene. Although the knockout-first allele was designed to interfere with splicing and thus disrupt gene function, the En2 sequence has been reported to be transcribed within the host gene mRNA due to a cryptic splice site within the En2 sequence which allows splicing to the next exon of the host gene. In some circumstances, this has the potential to permit translation of a mutant protein. Here, we describe our computational analysis of all the mouse protein-coding genes with established knockout-first embryonic stem cell lines, and our predictions of their transcription outcome should the En2 sequence be included. As part of the large-scale mutagenesis program, mutant mice underwent a broad phenotyping screen, and their phenotypes are available. No wide-scale effects on mouse phenotypes reported were found as a result of the predicted En2 insertion. However, the En2 insertion was found experimentally in the transcripts of 24 of 35 mutant alleles examined, including the five already described, two with evidence of readthrough. Splicing from the cryptic splice site also has the potential to disrupt expression of the lacZ reporter gene. It is recommended that mutant transcripts be checked for this insertion as well as for leaky transcription in studies involving knockout-first alleles.
{"title":"Investigating the effects of a cryptic splice site in the En2 splice acceptor sequence used in the IKMC knockout-first alleles.","authors":"Prerna Nair, Karen P Steel, Morag A Lewis","doi":"10.1007/s00335-024-10071-2","DOIUrl":"https://doi.org/10.1007/s00335-024-10071-2","url":null,"abstract":"<p><p>Targeted mouse mutants are a common tool used to investigate gene function. The International Knockout Mouse Consortium undertook a large-scale screen of mouse mutants, making use of the knockout-first allele design that contains the En2 splice acceptor sequence coupled to the lacZ reporter gene. Although the knockout-first allele was designed to interfere with splicing and thus disrupt gene function, the En2 sequence has been reported to be transcribed within the host gene mRNA due to a cryptic splice site within the En2 sequence which allows splicing to the next exon of the host gene. In some circumstances, this has the potential to permit translation of a mutant protein. Here, we describe our computational analysis of all the mouse protein-coding genes with established knockout-first embryonic stem cell lines, and our predictions of their transcription outcome should the En2 sequence be included. As part of the large-scale mutagenesis program, mutant mice underwent a broad phenotyping screen, and their phenotypes are available. No wide-scale effects on mouse phenotypes reported were found as a result of the predicted En2 insertion. However, the En2 insertion was found experimentally in the transcripts of 24 of 35 mutant alleles examined, including the five already described, two with evidence of readthrough. Splicing from the cryptic splice site also has the potential to disrupt expression of the lacZ reporter gene. It is recommended that mutant transcripts be checked for this insertion as well as for leaky transcription in studies involving knockout-first alleles.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-29DOI: 10.1007/s00335-024-10072-1
Sabine M Hölter, Lillian Garrett, Sebastian Bludau, Katrin Amunts
{"title":"Digital tools of analysis and data integration facilitate synergy between mouse and human brain research and enable translation.","authors":"Sabine M Hölter, Lillian Garrett, Sebastian Bludau, Katrin Amunts","doi":"10.1007/s00335-024-10072-1","DOIUrl":"https://doi.org/10.1007/s00335-024-10072-1","url":null,"abstract":"","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-20DOI: 10.1007/s00335-024-10070-3
Yuksel Agca, James Amos-Landgraf, Renee Araiza, Jennifer Brennan, Charisse Carlson, Dominic Ciavatta, Dave Clary, Craig Franklin, Ian Korf, Cathleen Lutz, Terry Magnuson, Fernando Pardo-Manuel de Villena, Oleg Mirochnitchenko, Samit Patel, Dan Port, Laura Reinholdt, K C Kent Lloyd
Now in its 25th year, the Mutant Mouse Resource and Research Center (MMRRC) consortium continues to serve the United States and international biomedical scientific community as a public repository and distribution archive of laboratory mouse models of human disease for research. Supported by the National Institutes of Health (NIH), the MMRRC consists of 4 regionally distributed and dedicated vivaria, offices, and specialized laboratory facilities and an Informatics Coordination and Service Center (ICSC). The overarching purpose of the MMRRC is to facilitate groundbreaking biomedical research by offering an extensive repertoire of mutant mice that are essential for advancing the understanding of human physiology and disease. The function of the MMRRC is to identify, acquire, evaluate, characterize, cryopreserve, and distribute mutant mouse strains to qualified biomedical investigators around the nation and the globe. Mouse strains accepted from the research community are held to the highest scientific standards to optimize reproducibility and enhance scientific rigor and transparency. All submitted strains are thoroughly reviewed, documented, and validated using extensive scientific quality control measures. In addition, the MMRRC conducts resource-related research on cryopreservation, mouse genetics, environmental conditions, and other topics that enhance operations of the MMRRC. Today, the MMRRC maintains an archive of mice, cryopreserved embryos and sperm, embryonic stem (ES) cell lines, and murine hybridomas for nearly 65,000 alleles. Since its inception, the MMRRC has fulfilled more than 20,000 orders from 13,651 scientists at 8441 institutions worldwide. The MMRRC also provides numerous services to assist researchers, including scientific consultation, technical assistance, genetic assays, microbiome analysis, analytical phenotyping, pathology, cryorecovery, husbandry, breeding and colony management, infectious disease surveillance, and disease modeling. The ICSC coordinates MMRRC operations, interacts with researchers, and manages the website (mmrrc.org) and online catalogue. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest scientific standards while submitting investigators benefit by having their mouse strains cryopreserved, protected, and distributed in compliance with NIH policies.
{"title":"The mutant mouse resource and research center (MMRRC) consortium: the US-based public mouse repository system.","authors":"Yuksel Agca, James Amos-Landgraf, Renee Araiza, Jennifer Brennan, Charisse Carlson, Dominic Ciavatta, Dave Clary, Craig Franklin, Ian Korf, Cathleen Lutz, Terry Magnuson, Fernando Pardo-Manuel de Villena, Oleg Mirochnitchenko, Samit Patel, Dan Port, Laura Reinholdt, K C Kent Lloyd","doi":"10.1007/s00335-024-10070-3","DOIUrl":"https://doi.org/10.1007/s00335-024-10070-3","url":null,"abstract":"<p><p>Now in its 25th year, the Mutant Mouse Resource and Research Center (MMRRC) consortium continues to serve the United States and international biomedical scientific community as a public repository and distribution archive of laboratory mouse models of human disease for research. Supported by the National Institutes of Health (NIH), the MMRRC consists of 4 regionally distributed and dedicated vivaria, offices, and specialized laboratory facilities and an Informatics Coordination and Service Center (ICSC). The overarching purpose of the MMRRC is to facilitate groundbreaking biomedical research by offering an extensive repertoire of mutant mice that are essential for advancing the understanding of human physiology and disease. The function of the MMRRC is to identify, acquire, evaluate, characterize, cryopreserve, and distribute mutant mouse strains to qualified biomedical investigators around the nation and the globe. Mouse strains accepted from the research community are held to the highest scientific standards to optimize reproducibility and enhance scientific rigor and transparency. All submitted strains are thoroughly reviewed, documented, and validated using extensive scientific quality control measures. In addition, the MMRRC conducts resource-related research on cryopreservation, mouse genetics, environmental conditions, and other topics that enhance operations of the MMRRC. Today, the MMRRC maintains an archive of mice, cryopreserved embryos and sperm, embryonic stem (ES) cell lines, and murine hybridomas for nearly 65,000 alleles. Since its inception, the MMRRC has fulfilled more than 20,000 orders from 13,651 scientists at 8441 institutions worldwide. The MMRRC also provides numerous services to assist researchers, including scientific consultation, technical assistance, genetic assays, microbiome analysis, analytical phenotyping, pathology, cryorecovery, husbandry, breeding and colony management, infectious disease surveillance, and disease modeling. The ICSC coordinates MMRRC operations, interacts with researchers, and manages the website (mmrrc.org) and online catalogue. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest scientific standards while submitting investigators benefit by having their mouse strains cryopreserved, protected, and distributed in compliance with NIH policies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mammalian genome research has conventionally involved mice and rats as model organisms for humans. Given the recent advances in life science research, to understand complex and higher-order biological phenomena and to elucidate pathologies and develop therapies to promote human health and overcome diseases, it is necessary to utilize not only mice and rats but also other bioresources such as standardized genetic materials and appropriate cell lines in order to gain deeper molecular and cellular insights. The Japanese bioresource infrastructure program called the National BioResource Project (NBRP) systematically collects, preserves, controls the quality, and provides bioresources for use in life science research worldwide. In this review, based on information from a database of papers related to NBRP bioresources, we present the bioresources that have proved useful for mammalian genome research, including mice, rats, other animal resources; DNA-related materials; and human/animal cells and microbes.
{"title":"Mammalian genome research resources available from the National BioResource Project in Japan","authors":"Saori Mizuno-Iijima, Shoko Kawamoto, Masahide Asano, Tomoji Mashimo, Shigeharu Wakana, Katsuki Nakamura, Ken-ichi Nishijima, Hitoshi Okamoto, Kuniaki Saito, Sawako Yoshina, Yoshihiro Miwa, Yukio Nakamura, Moriya Ohkuma, Atsushi Yoshiki","doi":"10.1007/s00335-024-10063-2","DOIUrl":"https://doi.org/10.1007/s00335-024-10063-2","url":null,"abstract":"<p>Mammalian genome research has conventionally involved mice and rats as model organisms for humans. Given the recent advances in life science research, to understand complex and higher-order biological phenomena and to elucidate pathologies and develop therapies to promote human health and overcome diseases, it is necessary to utilize not only mice and rats but also other bioresources such as standardized genetic materials and appropriate cell lines in order to gain deeper molecular and cellular insights. The Japanese bioresource infrastructure program called the National BioResource Project (NBRP) systematically collects, preserves, controls the quality, and provides bioresources for use in life science research worldwide. In this review, based on information from a database of papers related to NBRP bioresources, we present the bioresources that have proved useful for mammalian genome research, including mice, rats, other animal resources; DNA-related materials; and human/animal cells and microbes.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}