TSH Hypersecretion in WKY: Positional Candidate Analysis

WKY 中的 TSH 分泌过多：候选位置分析

• 批准号: 6552292
• 负责人: AMBER E BAUM
• 金额: $ 2.49万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6552292
• 关键词: behavior disorders; behavioral /social science research tag; behavioral genetics; endocrine disorder; gene expression; genetic strain; hypothalamic pituitary axis; laboratory rat; linkage mapping; molecular biology information system; open field behavior; pituitary thyroid axis; predoctoral investigator; quantitative trait loci; radioimmunoassay; thyrotropin

DESCRIPTION (provided by applicant): The high comorbidity between hypo- and hyperthyroidism and depressive disorders illustrates the influence of hypothalamic-pituitary-thyroid (HPT) axis function on behavior. The inbred Wistar-Kyoto (WKY) rat strain has persistently elevated TSH despite elevated thyroid hormone levels and normal negative feedback to the pituitary. Also, WKY are hypoactive in a variety of behavioral tests, including the open-field test. The strain is thus an excellent model for dissecting the relationships between multigenic behavioral traits and complex hormonal control systems using forward genetics. Genetic architectures of these traits will be investigated with quantitative trait locus (QTL) analysis. An F2 intercross population has been created from reciprocal crosses between WKY and the genetically, hormonally and behaviorally polymorphic Fischer-344 strain. The WKYxF344 F2 generation is sufficient to segregate phenotypic traits and create a linkage map to perform a QTL analysis. By demonstrating an association between an extreme expression of these phenotypes and marker alleles whose genetic map position is known, loci will be mapped to specific regions of individual chromosomes, and commonalities between the behavioral and hormonal traits? genetic architectures will be revealed. Significant loci of interest will be introgressed into congenic strains using marker-and phenotype-assisted selection, which will confirm the locus? role in the phenotype and permit its further analysis in isolation from other segregating loci that may modify its expression. The loci will also be analyzed using a positional candidate approach utilizing homology maps linking rat, mouse and human genomes. These experiments will contribute to the understanding of HPT regulation, and also illuminate any genetic links that may exist between these phenotypes.

描述（由申请人提供）：低剂量和低剂量之间的高共病率 甲状腺功能亢进症和抑郁症的影响，说明了 下丘脑-垂体-甲状腺（HPT）轴功能对行为的影响。近交 Wistar-Kyoto（WKY）大鼠品系尽管TSH升高， 甲状腺激素水平和对垂体的正常负反馈。另外，WKY 在各种行为测试中表现不活跃，包括旷场测试。 因此，该菌株是一个很好的模型，用于解剖 多基因行为性状和复杂的激素控制系统， 遗传学这些性状的遗传结构将进行研究， 数量性状基因座（QTL）分析。一个F2杂交群体， 从WKY和基因上，生殖上， 行为多态性Fischer-344菌株。WKYxF 344 F2代是 足以分离表型性状并创建连锁图以进行 QTL分析。通过展示极端表达与 这些表型和遗传图谱位置已知的标记等位基因， 将被映射到单个染色体的特定区域， 行为特征和荷尔蒙特征之间的联系基因结构将是 揭示将感兴趣的重要基因座渗入同源基因组中。 菌株使用标记和表型辅助选择，这将确认 轨迹？在表型中的作用，并允许其进一步分析， 其他分离基因座可以改变其表达。这些位点也将是 使用位置候选方法进行分析，所述位置候选方法利用同源图连接 大鼠、小鼠和人类基因组。这些实验将有助于 了解HPT调控，并阐明任何可能 存在于这些表型之间。