GENETIC CHARACTERIZATION OF THE HYPOTRICHOTIC MUTATION

缺毛突变的遗传特征

• 批准号: 2865131
• 负责人: THOMAS R KING
• 金额: $ 1.15万
• 依托单位: CENTRAL CONNECTICUT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2865131
• 关键词: autosomal recessive trait; developmental genetics; gene expression; gene interaction; gene mutation; genetic disorder; genetic mapping; genetic markers; genotype; hair; histology; laboratory rat; linkage mapping; molecular cloning; phenotype; polymerase chain reaction; skin disorder

DESCRIPTION: A spontaneous hypotrichotic mutant, characterized by the partial or complete absence of hair over most of the body, was discovered in Dr. King's colony of albino laboratory rats. Preliminary data demonstrate that the trait is inherited as an autosomal recessive gene, provisionally named shorn (shn), that is not allelic with any of the other known hypotrichotic mutations in rats. Shn maps to rat Chromosome (Chr) 10, which, excepting rnu, does not include any other named loci that are known to affect coat morphology. Homologous regions of the mouse genome also lack loci that are known to cause recessive hypotrichosis. The shn mutation therefore appears to identify a new gene that is essential for the normal development or maintenance of mammalian skin and hair. To advance the understanding of the shn gene's normal role in development, Dr. King proposes to characterize the shn mutation both genotypically and phenotypically. At the genotypic level of investigation, he aims to produce a fine-structure genetic map of the region around shn. Toward this aim, he will conduct a backcross of shn/+ F1 rats that are heterozygous for a large number of visible, biochemical, and PCR-scorable DNA markers. Analysis of about 250 progeny from this backcross will allow generation of a high-resolution, high-density genetic map of the region including and surrounding shn. This fine-structure genetic map, while advancing the genetic characterization of a 20-30 cM region of the rat genome, will facilitate identification of probes and candidates for the shn gene. At the phenotypic level, he proposes to carry out biochemical and histological comparisons between mutant and non-mutant testcross siblings. The biochemical analysis will focus on gene products known to be controlled by loci mapping in the same region as shn. Histological analysis of skin and other tissues may reveal pleiotropic effects of the mutation, and could help to implicate particular cell types, biomolecules, or a particular time or process involved in the development of the mutant phenotype. The genotypic and phenotypic investigations are expected to result in the identification of the shn gene, which in turn could lead to studies on its role in the normal development of mammalian skin and hair.

描述：一种自发性低血糖突变体，其特征为： 在身体的大部分部位部分或完全没有毛发， 博士国王的白化病实验鼠群。 初步数据显示， 该性状是作为常染色体隐性基因遗传的，暂时性的， 而所谓的“知”，就是“知”，就是“知”，就是“知”。 在大鼠中的低血糖突变。 Shn定位于大鼠染色体（Chr）10， 除了rnu，不包括任何其他已知的命名基因座， 以影响涂层形态。 小鼠基因组的同源区域也缺乏 已知会导致隐性脑下垂的基因座。 shn突变 因此，似乎确定了一个新的基因，是必不可少的正常 哺乳动物皮肤和毛发的发育或维持。 推进 了解shn基因在发育中的正常作用，金博士 建议在基因型和 表型上 在基因型水平的调查，他的目的是生产 shn周围区域的精细结构遗传图。 为了实现这一目标，他 将进行shn/+ F1大鼠的回交，这些大鼠对于大的 可见的、生物化学的和PCR可评分的DNA标记物的数量。 分析 来自该回交的约250个后代将允许产生 该地区的高分辨率，高密度遗传图，包括和 周围shn。 这种精细结构的遗传图谱，同时推进了 大鼠基因组20-30 cM区域的遗传表征，将 有助于鉴定SHN基因的探针和候选物。 在表型水平上，他建议进行生物化学和 突变和非突变测交同胞之间的组织学比较。 生化分析将集中在已知受控制的基因产物上 通过在与SHN相同的区域中的基因座作图。 皮肤组织学分析 和其他组织可能揭示了突变的多效性效应， 有助于推断特定细胞类型、生物分子或特定时间 或参与突变表型发展的过程。 的 基因型和表型研究预计将导致 shn基因的鉴定，这反过来又可能导致对其 在哺乳动物皮肤和毛发的正常发育中的作用。