Rat hypodactyly (hd) mutation is characterized by abnormal spermatogenesis and sperm decapitation, limb malformation (missing digits II and III) and growth retardation. We have previously reported centrobin (centrosome BRCA2-interacting protein) truncation at the C-terminus in the hd mutant. Here, we report data from a transgenic rescue experiment carried out to determine a role of centrobin in pathogenesis of hd. The transgenic construct, consisting of full-length-coding cDNA linked to a ubiquitous strong promoter/enhancer combination, was inserted to chromosome 16 into a LINE repeat. No known gene is present in the vicinity of the insertion site. Transgenic centrobin was expressed in all tissues tested, including testis. Transgenic animals show normal body weight and limb morphology as well as average weight of testis and epididymis. Yet, abnormal spermatogenesis and sperm decapitation persisted in the transgenic animals. Western blotting showed the coexistence of full-length and truncated or partially degraded centrobin in sperm of the rescued transgenic animals. Immunocytochemistry showed a buildup of centrobin and ODF2 (outer dense fiber 2) at the sperm decapitation site in the hd mutant and rescued transgenic rats. Additional findings included bulge-like formations and thread-like focal dissociations along the sperm flagellum and the organization of multiple whorls of truncated sperm flagella in the epididymal lumen. We conclude that centrobin is essential for normal patterning of the limb autopod. Centrobin may be required for stabilizing the attachment of the sperm head to flagellum and for maintaining the structural integrity of the sperm flagellum. We postulate that the presence of truncated centrobin, coexisting with full-length centrobin, together with incorrect timing of transgenic centrobin expression may hamper the rescue of fertility in hd male rats.

• MeSH
• epididymis patologie   MeSH
• exprese genu MeSH
• fertilita genetika   MeSH
• homeodoménové proteiny genetika   MeSH
• krysa rodu Rattus MeSH
• mutace * MeSH
• myši MeSH
• potkani transgenní MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• proteiny teplotního šoku metabolismus   MeSH
• spermie růst a vývoj   metabolismus   MeSH
• testis patologie   MeSH
• transport proteinů MeSH
• velikost orgánu genetika   MeSH
• vrozené deformity končetin genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• Cntrob protein, rat MeSH Prohlížeč
• homeobox protein HOXA13 MeSH Prohlížeč
• homeodoménové proteiny MeSH
• Odf2 protein, rat MeSH Prohlížeč
• proteiny buněčného cyklu MeSH
• proteiny teplotního šoku MeSH