Rat hd mutation reveals an essential role of centrobin in spermatid head shaping and assembly of the head-tail coupling apparatus.
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.
Liska
Frantisek
F
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague, Praha, Czech Republic. frantisek.liska@lf1.cuni.cz
Gosele
Claudia
C
Rivkin
Eugene
E
Tres
Laura
L
Cardoso
M Cristina
MC
Domaing
Petra
P
Krejcí
Eliska
E
Snajdr
Pavel
P
Lee-Kirsch
Min Ae
MA
de Rooij
Dirk G
DG
Rooij
Dirk G de
DG
Kren
Vladimír
V
Krenová
Drahomíra
D
Kierszenbaum
Abraham L
AL
Hubner
Norbert
N
D000818:Animals; D026481:Blotting, Far-Western; D018797:Cell Cycle Proteins / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics; D004822:Epididymis / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005801:Genes, Homeobox / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D007438:Introns / Q000235:genetics; D053555:Keratin-5 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013077:Sperm Head / Q000378:metabolism*; D013082:Sperm Tail / Q000378:metabolism*; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*
D018797:Cell Cycle Proteins; C583842:Cntrob protein, rat; D018398:Homeodomain Proteins; D053555:Keratin-5