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26 August 2009 Rat hd Mutation Reveals an Essential Role of Centrobin in Spermatid Head Shaping and Assembly of the Head-Tail Coupling Apparatus
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Abstract

The hypodactylous (hd) locus impairs limb development and spermatogenesis, leading to male infertility in rats. We show that the hd mutation is caused by an insertion of an endogenous retrovirus into intron 10 of the Cntrob gene. The retroviral insertion in hd mutant rats disrupts the normal splicing of Cntrob transcripts and results in the expression of a truncated protein. During the final phase of spermiogenesis, centrobin localizes to the manchette, centrosome, and the marginal ring of the spermatid acroplaxome, where it interacts with keratin 5-containing intermediate filaments. Mutant spermatids show a defective acroplaxome marginal ring and separation of the centrosome from its normal attachment site of the nucleus. This separation correlates with a disruption of head-tail coupling apparatus, leading to spermatid decapitation during the final step of spermiogenesis and the absence of sperm in the epididymis. Cntrob may represent a novel candidate gene for presently unexplained hereditary forms of teratozoospermia and the “easily decapitated sperm syndrome” in humans.

František Liška, Claudia Gosele, Eugene Rivkin, Laura Tres, M. Cristina Cardoso, Petra Domaing, Eliška Krejčí, Pavel Šnajdr, Min Ae Lee-Kirsch, Dirk G. de Rooij, Vladimír Křen, Drahomíra Křenová, Abraham L. Kierszenbaum, and Norbert Hubner "Rat hd Mutation Reveals an Essential Role of Centrobin in Spermatid Head Shaping and Assembly of the Head-Tail Coupling Apparatus," Biology of Reproduction 81(6), 1196-1205, (26 August 2009). https://doi.org/10.1095/biolreprod.109.078980
Received: 22 May 2009; Accepted: 1 July 2009; Published: 26 August 2009
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