Pub Date : 2025-12-18DOI: 10.1038/s41684-025-01664-8
Zachary McAdams, Kevin Gustafson, Aaron Ericsson
{"title":"Biological and technical variability in mouse microbiota analysis and implications for sample size determination","authors":"Zachary McAdams, Kevin Gustafson, Aaron Ericsson","doi":"10.1038/s41684-025-01664-8","DOIUrl":"https://doi.org/10.1038/s41684-025-01664-8","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"155 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1038/s41684-025-01650-0
Kirtan Joshi, Kanve N. Suvilesh, Nagabhishek Sirpu Natesh, Yariswamy Manjunath, Jared Coberly, Sarah Schlink, Jeffrey R. Kunin, Randall S. Prather, Kristin Whitworth, Benjamin Nelson, Jeffrey N. Bryan, Timothy Hoffman, Mojgan Golzy, Murugesan Raju, Emma Teixeiro, Bhanu P. Telugu, Jussuf T. Kaifi, Satyanarayana Rachagani
There remains a need for animal models with human translatability in lung cancer (LC) research. Findings in pigs can have a substantial impact owing to their similar anatomy and physiology to humans. Here we present a bronchoscopically induced LC model in Oncopigs carrying inducible KRASG12D and TP53R167H mutations. A total of 12 Oncopigs underwent 29 injections via flexible bronchoscopy: 18 adenovirus–Cre recombinase gene (AdCre) inductions were performed endobronchially ( n = 6) and transbronchially ( n = 12), and 11 control injections were performed without AdCre. Oncopigs underwent serial chest CT with clinical follow-up for 29 weeks. Lung and organ tissues underwent histopathology, immunohistochemistry and RNA sequencing with comparative analysis to human LC data. All 18 sites of AdCre injections had lung consolidations on computed tomography imaging. Inductions led to an overall success rate of 77.8%, including both invasive cancer (61.1%) and carcinoma in situ (16.7%). Transbronchial injections led to histopathologic invasive cancer and/or carcinoma in situ in 11/12 (91.7%) and invasive cancer in 8/12 (66.6%). Endobronchial inductions led to invasive cancer in 3/6 (50%). A soft tissue metastasis was observed in one Oncopig. Immunohistochemistry confirmed the expression of Pan-Cytokeratin (Pan-CK) + in epithelial cancer cells, with macrophage and T cell infiltration in the tumor microenvironment. Transcriptome comparison showed 54.3% overlap with human LC, while KRAS-mutant mouse LC had 29.88% overlap with human LC. The immunocompetent Oncopig model has a high rate of LC following bronchoscopic transbronchial induction. An overlap of the Oncopig LC transcriptome with the human LC transcriptome was noted. This pig model of LC is expected to have high clinical translatability.
{"title":"Characterization of a bronchoscopically induced transgenic lung cancer pig model for human translatability","authors":"Kirtan Joshi, Kanve N. Suvilesh, Nagabhishek Sirpu Natesh, Yariswamy Manjunath, Jared Coberly, Sarah Schlink, Jeffrey R. Kunin, Randall S. Prather, Kristin Whitworth, Benjamin Nelson, Jeffrey N. Bryan, Timothy Hoffman, Mojgan Golzy, Murugesan Raju, Emma Teixeiro, Bhanu P. Telugu, Jussuf T. Kaifi, Satyanarayana Rachagani","doi":"10.1038/s41684-025-01650-0","DOIUrl":"https://doi.org/10.1038/s41684-025-01650-0","url":null,"abstract":"There remains a need for animal models with human translatability in lung cancer (LC) research. Findings in pigs can have a substantial impact owing to their similar anatomy and physiology to humans. Here we present a bronchoscopically induced LC model in Oncopigs carrying inducible <jats:italic>KRAS</jats:italic> <jats:sup> <jats:italic>G12D</jats:italic> </jats:sup> and <jats:italic>TP53</jats:italic> <jats:sup> <jats:italic>R167H</jats:italic> </jats:sup> mutations. A total of 12 Oncopigs underwent 29 injections via flexible bronchoscopy: 18 adenovirus–Cre recombinase gene (AdCre) inductions were performed endobronchially ( <jats:italic>n</jats:italic> = 6) and transbronchially ( <jats:italic>n</jats:italic> = 12), and 11 control injections were performed without AdCre. Oncopigs underwent serial chest CT with clinical follow-up for 29 weeks. Lung and organ tissues underwent histopathology, immunohistochemistry and RNA sequencing with comparative analysis to human LC data. All 18 sites of AdCre injections had lung consolidations on computed tomography imaging. Inductions led to an overall success rate of 77.8%, including both invasive cancer (61.1%) and carcinoma in situ (16.7%). Transbronchial injections led to histopathologic invasive cancer and/or carcinoma in situ in 11/12 (91.7%) and invasive cancer in 8/12 (66.6%). Endobronchial inductions led to invasive cancer in 3/6 (50%). A soft tissue metastasis was observed in one Oncopig. Immunohistochemistry confirmed the expression of Pan-Cytokeratin (Pan-CK) <jats:sup>+</jats:sup> in epithelial cancer cells, with macrophage and T cell infiltration in the tumor microenvironment. Transcriptome comparison showed 54.3% overlap with human LC, while KRAS-mutant mouse LC had 29.88% overlap with human LC. The immunocompetent Oncopig model has a high rate of LC following bronchoscopic transbronchial induction. An overlap of the Oncopig LC transcriptome with the human LC transcriptome was noted. This pig model of LC is expected to have high clinical translatability.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"156 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1038/s41684-025-01652-y
Hernan Baldassarre,Werner G Glanzner,Karina Gutierrez,Reesha Raja,Albert H K Fok,Abigail Shea,Anne Pellegrin,Ioan Cozma,Lucie Côté,Keith Murai,Vilceu Bordignon
Marmosets are a valuable model for studying human disorders, but developing specific genetic models requires efficient protocols for embryo genomic manipulation. Although marmoset embryos have been produced in vitro, oocyte retrieval traditionally involves extended recombinant human follicle-stimulating hormone (FSH) treatment (9-10 days), surgical laparotomy and ovarian exposure, limiting repeat procedures. Here we evaluated a simpler, cost-effective ovarian stimulation protocol using porcine pituitary FSH, combined with laparoscopic ovum pick-up (LOPU), for in vitro production of marmoset embryos via in vitro fertilization (IVF) and somatic cell nuclear transfer. A total of 3,922 oocytes were retrieved from 129 LOPU procedures, averaging 30.4 oocytes per LOPU, with 85.5% (26.0 per LOPU) graded as viable. The procedure was safe, with no adverse effects observed in ovaries or fimbria after up to nine LOPU sessions. Most collected oocytes were meiotically immature and matured in vitro before use. Following IVF, approximately 40% of oocytes cleaved, and 40% of cleaved embryos developed to the expanded blastocyst stage. LOPU-derived oocytes also supported somatic cell nuclear transfer, with 69.8% of embryos cleaving and 21.8% forming blastocysts. IVF-derived blastocyst quality was assessed by total cell count, immunodetection of SOX2 (inner cell mass) and CDX2 (trophectoderm), and cryotolerance. Embryo transfer to recipients resulted in successful live births. These findings demonstrate that a simplified pituitary FSH protocol followed by LOPU is an efficient, less invasive and safe method for retrieving developmentally competent marmoset oocytes, offering a promising approach for advancing marmoset-based research in disease modeling and reproductive biotechnology.
{"title":"Efficient production of common marmoset embryos with in vitro fertilization and somatic cell nuclear transfer following optimized hormonal stimulation and laparoscopic oocyte collection.","authors":"Hernan Baldassarre,Werner G Glanzner,Karina Gutierrez,Reesha Raja,Albert H K Fok,Abigail Shea,Anne Pellegrin,Ioan Cozma,Lucie Côté,Keith Murai,Vilceu Bordignon","doi":"10.1038/s41684-025-01652-y","DOIUrl":"https://doi.org/10.1038/s41684-025-01652-y","url":null,"abstract":"Marmosets are a valuable model for studying human disorders, but developing specific genetic models requires efficient protocols for embryo genomic manipulation. Although marmoset embryos have been produced in vitro, oocyte retrieval traditionally involves extended recombinant human follicle-stimulating hormone (FSH) treatment (9-10 days), surgical laparotomy and ovarian exposure, limiting repeat procedures. Here we evaluated a simpler, cost-effective ovarian stimulation protocol using porcine pituitary FSH, combined with laparoscopic ovum pick-up (LOPU), for in vitro production of marmoset embryos via in vitro fertilization (IVF) and somatic cell nuclear transfer. A total of 3,922 oocytes were retrieved from 129 LOPU procedures, averaging 30.4 oocytes per LOPU, with 85.5% (26.0 per LOPU) graded as viable. The procedure was safe, with no adverse effects observed in ovaries or fimbria after up to nine LOPU sessions. Most collected oocytes were meiotically immature and matured in vitro before use. Following IVF, approximately 40% of oocytes cleaved, and 40% of cleaved embryos developed to the expanded blastocyst stage. LOPU-derived oocytes also supported somatic cell nuclear transfer, with 69.8% of embryos cleaving and 21.8% forming blastocysts. IVF-derived blastocyst quality was assessed by total cell count, immunodetection of SOX2 (inner cell mass) and CDX2 (trophectoderm), and cryotolerance. Embryo transfer to recipients resulted in successful live births. These findings demonstrate that a simplified pituitary FSH protocol followed by LOPU is an efficient, less invasive and safe method for retrieving developmentally competent marmoset oocytes, offering a promising approach for advancing marmoset-based research in disease modeling and reproductive biotechnology.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"148 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1038/s41684-025-01666-6
Ana Isabel Santos,Nuno Henrique Franco
{"title":"ETPLAS Conference: Shaping the future of LAS education and training.","authors":"Ana Isabel Santos,Nuno Henrique Franco","doi":"10.1038/s41684-025-01666-6","DOIUrl":"https://doi.org/10.1038/s41684-025-01666-6","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"49 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1038/s41684-025-01651-z
Nuno Henrique Franco, Otto Kalliokoski, Vootele Voikar
{"title":"The 2025 FELASA Congress in Athens: From Aristotle to AI","authors":"Nuno Henrique Franco, Otto Kalliokoski, Vootele Voikar","doi":"10.1038/s41684-025-01651-z","DOIUrl":"https://doi.org/10.1038/s41684-025-01651-z","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"187 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1038/s41684-025-01655-9
Alexandra Le Bras
{"title":"A zebrafish model of chronic heart failure","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01655-9","DOIUrl":"10.1038/s41684-025-01655-9","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 12","pages":"338-338"},"PeriodicalIF":3.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1038/s41684-025-01662-w
Alexandra Le Bras
{"title":"Central metabolic activity is preserved in aged mice","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01662-w","DOIUrl":"10.1038/s41684-025-01662-w","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 12","pages":"341-341"},"PeriodicalIF":3.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-025-01662-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1038/s41684-025-01647-9
Nataliia Shapovalova, Thorsten Buch, Heinrich Bollwein, Johannes vom Berg, Eleni Malama
Cryopreservation of spermatozoa can be used as a cost-effective way of preserving the ever-increasing number of genetically modified mouse lines. Nevertheless, discontinuing the breeding of a line or strain is only warranted after the quality control of cryopreserved sperm; the ability of sperm to survive the freezing–thawing process and produce well-developed embryos needs to be confirmed. In animal research husbandries, the fertility of frozen-thawed sperm is routinely tested using in vitro fertilization. However, this procedure requires euthanizing a considerable number of females to acquire a sufficient number of oocytes, contradicting the ‘reduction’ principle of the 3Rs (replacement, reduction and refinement). Therefore, the research community has an interest in replacing in vitro fertilization tests with proxies that can collectively characterize the fertilizing potential of mouse sperm. Methods such as computer-assisted sperm analysis and flow cytometry enable a precise and multiparametric approach to evaluate sperm quality, encompassing ‘traditional’ traits and the functional status of subcellular structures of sperm. Moreover, single-cell data can be processed with machine learning algorithms, offering a deeper insight into sperm physiology and functional heterogeneity. Despite the advancements made, many of these assays are still far from being used in mouse sperm quality control owing to their limited time- and cost-efficiency, the insufficiency of fertility validation studies, and the complex data analysis needed to identify fertility markers. The genetic and phenotypic diversity of different mouse strains and lines makes the establishment of a robust methodology for fertility prognostics even more challenging. Thus, this Review summarizes the available methods for assessing sperm functional characteristics in laboratory mice and discusses their contribution to fertility prognosis. Cryopreservation of spermatozoa preserves genetically modified mouse lines, but quality control is critical. Given that in vitro fertilization testing presents limitations, this Review explores other available methods to evaluate sperm quality.
{"title":"Beyond swimming: emerging parameters for predicting the fertility of mouse spermatozoa","authors":"Nataliia Shapovalova, Thorsten Buch, Heinrich Bollwein, Johannes vom Berg, Eleni Malama","doi":"10.1038/s41684-025-01647-9","DOIUrl":"10.1038/s41684-025-01647-9","url":null,"abstract":"Cryopreservation of spermatozoa can be used as a cost-effective way of preserving the ever-increasing number of genetically modified mouse lines. Nevertheless, discontinuing the breeding of a line or strain is only warranted after the quality control of cryopreserved sperm; the ability of sperm to survive the freezing–thawing process and produce well-developed embryos needs to be confirmed. In animal research husbandries, the fertility of frozen-thawed sperm is routinely tested using in vitro fertilization. However, this procedure requires euthanizing a considerable number of females to acquire a sufficient number of oocytes, contradicting the ‘reduction’ principle of the 3Rs (replacement, reduction and refinement). Therefore, the research community has an interest in replacing in vitro fertilization tests with proxies that can collectively characterize the fertilizing potential of mouse sperm. Methods such as computer-assisted sperm analysis and flow cytometry enable a precise and multiparametric approach to evaluate sperm quality, encompassing ‘traditional’ traits and the functional status of subcellular structures of sperm. Moreover, single-cell data can be processed with machine learning algorithms, offering a deeper insight into sperm physiology and functional heterogeneity. Despite the advancements made, many of these assays are still far from being used in mouse sperm quality control owing to their limited time- and cost-efficiency, the insufficiency of fertility validation studies, and the complex data analysis needed to identify fertility markers. The genetic and phenotypic diversity of different mouse strains and lines makes the establishment of a robust methodology for fertility prognostics even more challenging. Thus, this Review summarizes the available methods for assessing sperm functional characteristics in laboratory mice and discusses their contribution to fertility prognosis. Cryopreservation of spermatozoa preserves genetically modified mouse lines, but quality control is critical. Given that in vitro fertilization testing presents limitations, this Review explores other available methods to evaluate sperm quality.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 12","pages":"343-354"},"PeriodicalIF":3.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-025-01647-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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