BILE SALT COMPOSITION AND LEVELS IN BILE, SERUM, AND LIVER OF FIC1 MUTANT MICE

FIC1 突变小鼠胆汁、血清和肝脏中的胆汁盐组成和水平

• 批准号: 7724220
• 负责人: LAURA N BULL
• 金额: $ 0.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7724220
• 关键词: Bile fluid; Biological; Biological Assay; Cholates; Cholestasis; Chromosome Mapping; Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; Defect; Development; Disease; Equipment; Etiology; Funding; Genetic; Goals; Grant; Human; Institution; Liver; Mass Spectrum Analysis; Metabolism; Modeling; Mus; Mutant Strains Mice; Mutation; Orthologous Gene; Patients; Phenotype; Predisposition; Protocols documentation; Research; Research Personnel; Resources; Role; Serum; Source; United States National Institutes of Health; Work; bile salts; cholate; design; dietary supplements; mutant; trait

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have identified mutations of FIC1/ATP8B1 as underlying development of cholestasis in some patients. Subsequently, we generated a mouse bearing a mutation in the orthologous gene, as a model of FIC1/ATP8B1 disease. The phenotype of the homozygous Fic1/Atp8b1 mutant mouse differs depending upon background strain. An overall goal of our studies of the Fic1 mutant mouse is to perform genetic mapping to identify genetic modifiers of the murine Fic1 mutant phenotype; such studies will illuminate the biological role of Fic1 and its human ortholog, and may identify candidate susceptibility loci for development and progression of FIC1 disease, as well as more common disorders of complex etiology. To optimize strain choice and protocols for the genetic mapping studies, and to identify those traits for which phenotyping is most worthwhile during those studies, we are further characterizing the phenotypes of Fic1 mutant and wildtype mice of 3 strain backgrounds, after challenge with either control or cholate-supplemented diet. These studies will include analysis of bile salt quantity and composition in bile, serum, and possibly liver; as a fundamental defect in cholestatic disease is in metabolism and transport of bile salts, analysis of bile salts is key to our studies. The UCSF Mass Spectrometry Facility will assist us in this work by providing advice, helping us to design and implement optimal assay conditions, and providing access to the specialized equipment necessary to perform these analyses.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们已经将FIC1/ATP8B1的突变确定为某些患者的胆汁淤积的潜在发展。 随后，我们在直系同源基因中产生了一种轴承突变的小鼠，作为FIC1/ATP8B1疾病的模型。 纯合FIC1/ATP8B1突变小鼠的表型取决于背景应变。 我们对FIC1突变小鼠研究的总体目标是进行遗传图，以鉴定鼠FIC1突变体表型的遗传修饰符。这样的研究将阐明FIC1及其人类直系同源物的生物学作用，并可能确定候选人的易感性基因座在FIC1疾病的发展和发展以及复杂病因的更常见疾病中。 为了优化遗传学图研究的应变选择和方案，并确定在这些研究期间最有价值的表型的特征，我们正在进一步表征FIC1突变体的表型和具有3株菌株背景的野生型小鼠的表型，在对控制或挑选饮食的挑战之后。 这些研究将包括分析胆汁，血清以及可能的肝脏中的胆汁盐量和成分。作为胆汁淤积性疾病的根本缺陷是代谢和胆汁盐的运输，对胆汁盐的分析是我们研究的关键。 UCSF质谱设施将通过提供建议，帮助我们设计和实施最佳测定条件，并提供对执行这些分析所需的专业设备的访问权，从而帮助我们完成这项工作。