Hypopigmentation and Maternal-Zygotic Embryonic Lethality Caused by a Hypomorphic Mbtps1 Mutation in Mice

G3: Genes, Genomes, Genetics

Eva Marie Y. Moresco³  Xin Du³  Katharina Brandl³  Xiaohong Li³  Daniel L. Popkin³  Yu Xia³  Alana A. Shigeoka²  Karine Crozat³  Sophie Rutschmann³  Dianne B. McKay²  Jeffrey C. Hanselman¹  Bruce Beutler³ 

[1] Pfizer Global Research and Development, Department of Cardiovascular Pharmacology, Ann Arbor, Michigan 48105Pfizer Global Research and Development, Department of Cardiovascular Pharmacology, Ann Arbor, Michigan 48105Pfizer Global Research and Development, Department of Cardiovascular Pharmacology, Ann Arbor, Michigan 48105;Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037;Department of GeneticsDepartment of GeneticsDepartment of Genetics

关键词: pigmentation;    coat color;    site 1 protease;    cholesterol;    maternal-zygotic effect lethality;   

DOI  :  10.1534/g3.112.002196

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

The site 1 protease, encoded by Mbtps1, mediates the initial cleavage of site 2 protease substrates, including sterol regulatory element binding proteins and CREB/ATF transcription factors. We demonstrate that a hypomorphic mutation of Mbtps1 called woodrat (wrt) caused hypocholesterolemia, as well as progressive hypopigmentation of the coat, that appears to be mechanistically unrelated. Hypopigmentation was rescued by transgenic expression of wild-type Mbtps1, and reciprocal grafting studies showed that normal pigmentation depended upon both cell-intrinsic or paracrine factors, as well as factors that act systemically, both of which are lacking in wrt homozygotes. Mbtps1 exhibited a maternal-zygotic effect characterized by fully penetrant embryonic lethality of maternal-zygotic wrt mutant offspring and partial embryonic lethality (~40%) of zygotic wrt mutant offspring. Mbtps1 is one of two maternal-zygotic effect genes identified in mammals to date. It functions nonredundantly in pigmentation and embryogenesis.

【 授权许可】

Unknown