• PMID: 26496357
• Gene Name: POC1A
• Condition: Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

LINE-1 Mediated Insertion into Poc1a (Protein of Centriole 1 A) Causes Growth Insufficiency and Male Infertility in Mice

Geister KA, Brinkmeier ML, Cheung LY, Wendt J, Oatley MJ, Burgess DL, Kozloff KM, Cavalcoli JD, Oatley JM, Camper SA.

Skeletal dysplasias are a common, genetically heterogeneous cause of short stature that can result from disruptions in many cellular processes. We report the identification of the lesion responsible for skeletal dysplasia and male infertility in the spontaneous, recessive mouse mutant chagun. We determined that Poc1a, encoding protein of the centriole 1a, is disrupted by the insertion of a processed Cenpw cDNA, which is flanked by target site duplications, suggestive of a LINE-1 retrotransposon-mediated event. Mutant fibroblasts have impaired cilia formation and multipolar spindles. Male infertility is caused by defective spermatogenesis early in meiosis and progressive germ cell loss. Spermatogonial stem cell transplantation studies revealed that Poc1a is essential for normal function of both Sertoli cells and germ cells. The proliferative zone of the growth plate is small and disorganized because chondrocytes fail to re-align after cell division and undergo increased apoptosis. Poc1a and several other genes associated with centrosome function can affect the skeleton and lead to skeletal dysplasias and primordial dwarfisms. This mouse mutant reveals how centrosome dysfunction contributes to defects in skeletal growth and male infertility. FAU - Geister, Krista A AU - Geister KA AD - Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, United States of America. FAU - Brinkmeier, Michelle L AU - Brinkmeier ML AD - Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of America. FAU - Cheung, Leonard Y AU - Cheung LY AD - Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of America. FAU - Wendt, Jennifer AU - Wendt J AD - Roche NimbleGen, Inc., Research and Development, Madison, Wisconsin, United States of America. FAU - Oatley, Melissa J AU - Oatley MJ AD - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of America. FAU - Burgess, Daniel L AU - Burgess DL AD - Roche NimbleGen, Inc., Research and Development, Madison, Wisconsin, United States of America. FAU - Kozloff, Kenneth M AU - Kozloff KM AD - Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan, United States of America. FAU - Cavalcoli, James D AU - Cavalcoli JD AD - Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America. FAU - Oatley, Jon M AU - Oatley JM AD - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of America.