Zoological Research最新文献

Ischemic heart disease (IHD) remains a leading contributor to cardiovascular disease (CVD) worldwide. Despite advances in diagnostic and therapeutic approaches, translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application. Among these, porcine models have gained prominence due to their anatomical, physiological, immunological, and genomic similarities to humans. This review provides a comprehensive overview of current methodologies for establishing porcine IHD models, critically assesses emerging rehabilitative strategies, and outlines innovative therapeutic technologies, with the goal of guiding model selection and fostering the development of novel treatment strategies.

Pentadactyl limbs represent a conserved morphological feature among tetrapods, with anterior digits considered more important than posterior digits for refined movement. While posterior digit formation is governed by graded expression of the Shh and 5' Hox genes, the regulatory mechanisms underlying anterior digit development, especially digit I (DI), remain poorly defined. This study identified an anterior expression pattern of Zic3 in the limb buds of representative tetrapods, including humans, which exerted an inhibitory effect on skeletal development. Zic3 was highly expressed in the anterior region of limb buds at early developmental stages, with species-specific divergence emerging during later development. Overexpression of Zic3 significantly delayed chondrogenesis and ossification, leading to bone shortening but not loss. Furthermore, RNA sequencing demonstrated that Zic3 down-regulated key genes associated with skeletal development, including Cytl1, Sox9, Ihh, Ptch1, Runx2, and Wnt16. These findings demonstrate that Zic3 acts as a conserved inhibitor of anterior skeletal maturation and contributes to the molecular asymmetry of tetrapod limb development.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies. Among the genetic contributors to CP, the carboxypeptidase A1 p.Ser282Pro ( CPA1 ^S282P ) variant has been proposed to promote disease through misfolding-induced endoplasmic reticulum stress (ERS), although the broader pathogenic landscape remains incompletely defined. This study generated a rabbit model mimicking the human CPA1 ^S282P mutation using the SpRY-ABE-8.17 system. Homozygous CPA1 ^S282P rabbits exhibited characteristic human CP phenotypes following alcohol induction, including visceral pain, elevated serum lipase and amylase, inflammatory cell infiltration, and extensive pancreatic fibrosis. Biochemical analyses confirmed that the p.S282P mutation induced CPA1 misfolding and elevated the expression of ERS markers GRP78 and CHOP in both transfected HEK293T cells and homozygous mutant rabbits. Notably, the CPA1 ^S282P mutation markedly disrupted intra-pancreatic lipid homeostasis, contributing to the development of CP in mutant rabbits. This study successfully established the first rabbit model of CP that accurately recapitulates CP caused by a defined human point mutation. Additionally, this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism, offering a foundation for identifying novel therapeutic targets for human CP.

Flight feathers represent a hallmark innovation of avian evolution. Recent comparative genomic analyses identified a 284 bp avian-specific highly conserved element (ASHCE) located within the eighth intron of the SIM bHLH transcription factor 1 ( Sim1) gene, postulated to act as a cis-regulatory element governing flight feather morphogenesis. To investigate its functional significance, genome-edited (GE) primordial germ cell (PGC) lines carrying targeted ASHCE deletions were generated using CRISPR/Cas9-mediated editing, with germline chimeric males subsequently mated with wild-type (WT) hens to obtain GE progeny. The resulting GE chickens harbored 257-260 bp deletions, excising approximately half of the Sim1-ASHCE sequence. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) analysis showed an average 0.32-fold reduction in Sim1 expression in the forelimbs of GE embryos at day 8 (E8) compared to WT counterparts. Despite this, GE chickens developed structurally normal flight and tail feathers. In situ hybridization localized Sim1 expression to the posterior mesenchyme surrounding flight feather buds in E8 WT embryos, but not within the buds themselves. These results suggest that partial deletion of Sim1-ASHCE, despite diminishing Sim1 expression, does not disrupt flight feather formation. The excised region appears to possess enhancer activity toward Sim1 but is dispensable for flight feather development. Complete ablation of the ASHCE will be necessary to fully resolve the regulatory role of Sim1 in avian feather morphogenesis.

The immunomodulatory function of estrogen within the ovary remains a subject of ongoing debate, and the neonatal ovarian immune microenvironment, particularly its modulation by estrogen, has not been comprehensively characterized. In this study, the effects of 17β-estradiol (E ₂), a key regulator of immune function, were investigated using single-cell transcriptomic profiling of C57BL/6J neonatal mouse ovaries after E ₂ treatment. Results revealed dynamic alterations in the proportion of immune cell types after E ₂ treatment, accompanied by changes in cytokine and chemokine expression. Detailed analyses of gene expression, cell states, and developmental trajectories across distinct cell types indicated that E ₂ treatment influenced cell differentiation and development. Notably, E ₂ treatment reduced the abundance of macrophages and promoted a phenotypic transition from M1 to M2 macrophages. These findings demonstrate that the neonatal mouse ovarian immune microenvironment is sensitive to estrogenic modulation, which governs both the distribution and functional specialization of resident immune cells, offering novel mechanistic insights into the immunomodulatory roles of estrogen across various immune cell types.

Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have independently evolved specialized musk-secreting glands, representing a striking case of convergent evolution. Through an integrated multi-omics approach, this study identified cyclopentadecanone as a shared key metabolic precursor in musk from both forest musk deer and muskrat, although downstream metabolite profiles diverged between the two lineages. Single-cell RNA sequencing revealed that these specialized apocrine glands possessed unique secretory architecture and exhibited transcriptional profiles associated with periodic musk production, distinct from those in conventional apocrine glands. Convergent features were evident at the cellular level, where acinar, ductal, and basal epithelial subtypes showed parallel molecular signatures across both taxa. Notably, acinar cells in both species expressed common genes involved in fatty acid and glycerolipid metabolism (e.g., ACSBG1, HSD17B12, HACD2, and HADHA), suggesting a conserved molecular framework for musk precursor biosynthesis. Metagenomic analysis of musk samples further revealed parallel microbial community structures dominated by Corynebacterium and enriched in lipid metabolic pathways. These findings suggest multi-level convergence in musk biosynthesis, from molecular pathways to microbial communities, providing novel insights into mammalian chemical signaling and artificial musk production.

Coat color polymorphism in domestic animals provides a robust framework for elucidating mechanisms of species adaptation, domestication, and genomic diversity. Leiqiong cattle, a representative indicine breed from southern China, are predominantly yellow-coated, although a subset exhibits a solid black phenotype. To determine the genetic basis of this variation, a genome-wide association study (GWAS) was performed in 212 Leiqiong bulls. A pronounced association signal was detected on chromosome 6 within the fifth intron of the CORIN gene, providing the first evidence of the potential influence of CORIN on bovine coat color variation. Integration of these results with publicly available genomic datasets and haplotype analyses indicated that the yellow coat phenotype is derived from Indian indicine ancestry, whereas the black coat phenotype emerged through introgression from wild bovine lineages and artificial hybridization with Wagyu cattle. Comparative analysis of Indian indicine cattle with divergent coat colors revealed distinct LEF1 haplotypes within a shared CORIN background, suggesting an ancient and complex domestication history underlying coat color variation. These findings provide direct evidence that introgression has shaped phenotypic variation in East Asian cattle and offer novel insights into the genetic architecture of pigmentation, with implications for future breeding strategies.

Pigs have emerged as valuable large-animal models for cardiac xenotransplantation; however, the temporal dynamics of myocardial development in this species remains insufficiently defined. This study analyzed gene expression patterns across four key developmental stages (neonatal, juvenile, sexual maturity, and adulthood) to delineate the molecular mechanisms driving porcine myocardial development. Increases in heart weight were accompanied by proportional expansion of myocardial fiber area and chamber size, reflecting coordinated structural development. Transcriptomic profiling of myocardial tissue by RNA sequencing (RNA-seq) identified 2 189 differentially expressed genes (DEGs) across stage comparisons. Short time-series expression miner (STEM) analysis classified these DEGs into four major expression clusters enriched in pathways associated with myocardial development, immune responses, cell proliferation, and metabolic processes. Among 359 DEGs conserved across all developmental stages, six candidate genes were strongly associated with myocardial development. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) confirmed a significant correlation between the expression of these candidate genes and myocardial development in porcine tissue. These findings establish a transcriptomic framework for porcine myocardial maturation and provide a molecular basis for advancing cardiac xenotransplantation.

Cytoplasmic accumulation of TDP-43 is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. While current studies have primarily focused on gene regulation mediated by full-length nuclear TDP-43, the potential effects of cytoplasmic TDP-43 fragments remain less explored. Our previous findings demonstrated that primate-specific cleavage of TDP-43 contributes to its cytoplasmic localization, prompting further investigation into its pathological effects. In the cynomolgus monkey brain, we observed that mutant or truncated TDP-43 was transported onto the ribosome organelle. Ribosome-associated transcriptomic analysis revealed dysregulation of apoptosis- and lysosome-related genes, indicating that cytoplasmic TDP-43 induces neurotoxicity by binding to ribosomes and disrupting mRNA expression. These findings provide mechanistic insights into the gain-of-function effects of pathological TDP-43.