Hr突变体转基因小鼠的构建及其在毛发生长发育中表达调控的分子机制

Yuyi hairless mice were cultivated by our studying team. They were a kind of spontaneous mutation animals. A stop codon mutation was found in hairless gene (Hr) by our prophase research. Hair cycle was regulating by Hr gene. Hr protein was thyroid receptor transcription corepressor, and it played an important role in hair follicle cells proliferation, differentiation, apoptosis and keeping integrity of dermal papilla and epithelium structure. Gene locus mutation might lead to hairless in mice. With the former research foundation, our studying team analied the expression of Hr gene in molecular biological techniques by taking Yuyi hairless mice and Kunming mice as research object. We investigated the biological function of hr gene by establishing transgenic mouse model in prokaryon microinjection. We could research the gene espression changes in the skin tissue of hairless mice and normal mice in gene chip technology and proteomic techniques. We could understand expression regulation molecular mechanism in hair growth and development in Hr gene, and we also understand the generation mechanism of hairless. Our research results could provide basic information in etiology and molecular mechanism of alopecia and pelada in gene and protein level.

豫医无毛小鼠是课题组培育的一种自发性突变动物，前期研究在无毛基因（Hr）上发现了一个终止密码子突变。Hr基因调控毛发生长周期转换，其蛋白产物是甲状腺受体转录的辅阻遏物，对毛囊细胞增殖、分化和凋亡的平衡及保持毛乳头与上皮结构的完整性具有重要作用，基因位点的突变导致小鼠完全和持久的无毛。本课题在以往研究工作的基础上，以自发突变的豫医无毛小鼠和正常昆明小鼠为研究对象，采用分子生物学技术分析Hr基因的表达情况；采用原核显微注射技术建立Hr基因及其突变体转基因小鼠模型，探讨Hr基因的生物学功能；并采用基因芯片及蛋白组学技术研究正常和无毛小鼠皮肤组织中的基因表达变化，深入了解Hr基因在毛发生长发育中表达调控的分子机制，以及无毛表型产生的机理。预期本研究结果将从基因和蛋白水平为脱发、斑秃等毛发疾病的病因及其分子机制等方面的研究提供基础资料。

豫医无毛小鼠是课题组培育的一种自发性突变动物，前期研究在无毛基因（Hr）上发现了一个终止密码子突变。Hr基因调控毛发生长周期转换，其蛋白产物是甲状腺受体转录的辅阻遏物，对毛囊细胞增殖、分化和凋亡的平衡及保持毛乳头与上皮结构的完整性具有重要作用，基因位点的突变导致小鼠完全和持久的无毛。本课题在以往研究工作的基础上，以自发突变的豫医无毛小鼠和正常昆明小鼠为研究对象，采用分子生物学技术分析了Hr基因的表达情况；采用显微注射及TALEN基因修饰技术分别建立了Hr基因转基因小鼠和敲除小鼠，探讨了Hr基因的生物学功能；并采用荧光定量PCR、基因芯片及蛋白组学技术研究正常和无毛小鼠皮肤组织中的基因及蛋白的表达变化，深入了解Hr基因在毛发生长发育中表达调控的分子机制，以及无毛表型产生的机理。研究结果从基因和蛋白水平为脱发、斑秃等毛发疾病的病因及其分子机制等方面的研究提供了基础资料。