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CC BY V4.0, Open Access
Journal article
LINE-1 Mediated Insertion into Poc1a (Protein of Centriole 1 A) Causes Growth Insufficiency and Male Infertility in Mice
PLoS genetics, Vol.11(10), pp.e1005569-e1005569
10/2015
Handle:
https://hdl.handle.net/2376/105496
PMCID: PMC4619696
PMID: 26496357
Abstract
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.
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Details
- Title
- LINE-1 Mediated Insertion into Poc1a (Protein of Centriole 1 A) Causes Growth Insufficiency and Male Infertility in Mice
- Creators
- Krista A Geister - Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, United States of AmericaMichelle L Brinkmeier - Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of AmericaLeonard Y Cheung - Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of AmericaJennifer Wendt - Roche NimbleGen, Inc., Research and Development, Madison, Wisconsin, United States of AmericaMelissa J Oatley - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of AmericaDaniel L Burgess - Roche NimbleGen, Inc., Research and Development, Madison, Wisconsin, United States of AmericaKenneth M Kozloff - Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan, United States of AmericaJames D Cavalcoli - Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of AmericaJon M Oatley - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of AmericaSally A Camper - Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, United States of America; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of America
- Publication Details
- PLoS genetics, Vol.11(10), pp.e1005569-e1005569
- Academic Unit
- School of Molecular Biosciences
- Publisher
- United States
- Grant note
- R01 HD030428 / NICHD NIH HHS T32 GM007315 / NIGMS NIH HHS R01HD34283 / NICHD NIH HHS R01 HD061665 / NICHD NIH HHS P30 CA046592 / NCI NIH HHS R01HD30428 / NICHD NIH HHS R01 HD034283 / NICHD NIH HHS R01HD061665 / NICHD NIH HHS
- Identifiers
- 99900546945301842
- Language
- English
- Resource Type
- Journal article