Mouse Mutant Resource

描述（由申请人提供）：杰克逊实验室（JAX）的小鼠突变资源（MMR）的使命是为生物医学和生物学研究提供小鼠模型。自发突变仍然是人类疾病小鼠模型的主要来源。它们补充了特异性靶向突变，并且具有首先被生物医学相关表型识别的优势，并且不需要事先了解潜在基因。MMR项目的具体目标是：1)利用基于snp的作图和高通量测序（HTPS）鉴定具有可遗传表型的自发突变株的致病基因突变；2)通过定义其解剖、组织病理、生理和超微结构异常来表征新突变体的表型特征；3)通过发布新的突变体信息，将其作为冷冻配子或胚胎和DNA保存以供将来的分子分析，并将小鼠分发给其他研究者，为科学界提供资源；4)利用比较基因组杂交、RNASeq和改进的HTPS生物信息学分析方法提高致病突变的识别率。新的突变体是在JAX的大型育种菌落中发现的多型偏差，并通过确定遗传模式、测试具有产生相似表型的已知突变的等位基因、确定染色体位置以及使用外显子组或全基因组测序识别突变基因来确定遗传特征。通过观察其生长、生存能力、生育能力、寿命和行为以及定义其解剖、组织病理学和生理异常，每个新突变体都具有表型特征。对于那些具有模拟人类疾病表型的突变体，进行更深层次的表型分析以提高其价值。MMR团队在骨生物学、生殖学、一般组织病理学和神经病理学方面拥有专业知识；我们与其他领域的经验丰富的研究人员合作，包括听力、视觉和代谢组学。所有新的突变体都在同行评议的期刊上发表，或在MMR和JAX网站上展示，相关信息可通过小鼠基因组数据库获得。

DESCRIPTION (provided by applicant): The mission of the Mouse Mutant Resource (MMR) at The Jackson Laboratory (JAX) is to provide mouse models for biomedical and biological research. Spontaneous mutations continue to be a major source of mouse models for human disorders. They complement specifically targeted mutations and have the advantage that they are first recognized by biomedically-relevant phenotypes and do not require prior knowledge of the underlying genes. The specific objectives of the MMR program are to 1) identify the causative genetic mutation in spontaneous mutant strains with heritable phenotypes using SNP-based mapping and high throughput sequencing (HTPS); 2) characterize new mutants phenotypically by defining their anatomical, histopathological, physiological, and ultrastructural abnormalities; 3) provide resources to the scientific community by publishing information on new mutants, preserving them as frozen gametes or embryos and DNA for future molecular analysis, and distributing mice to other investigators, and 4) enhance the identification rate of causative mutations using comparative genome hybridization, RNASeq and improved bioinformatics analysis methods for HTPS. New mutants are discovered as pljienotypic deviants appearing in JAX's large breeding colonies and characterized genetically by determining mode of inheritance, testing for allelism with known mutations that produce similar phenotypes, determining chromosomal locations and identifying the mutated gene using exome or whole genome sequencing. Each new mutant is characterized phenotypically by observing its growth, viability, fertility, life span and behavior and by defining its anatomical, histopathological and physiological abnormalities. For those mutants with phenotypes that model human disorders, deeper phenotyping is carried out to enhance their value. The MMR team has expertise in bone biology, reproduction, general histopathology and neuropathology; we collaborate with experienced investigators in other fields including hearing, vision and metabolomics. All new mutants are published in peer-reviewed journals or presented on the MMR and JAX web sites, and related information is made available through the Mouse Genome Database.