Inactivation of CUG-BP1/CELF1 causes growth, viability, and spermatogenesis defects in mice.
CUG-BP1/CELF1 is a multifunctional RNA-binding protein involved in the regulation of alternative splicing and translation. To elucidate its role in mammalian development, we produced mice in which the Cugbp1 gene was inactivated by homologous recombination. These Cugbp1(-/-) mice were viable, although a significant portion of them did not survive after the first few days of life. They displayed growth retardation, and most Cugbp1(-/-) males and females exhibited impaired fertility. Male infertility was more thoroughly investigated. Histological examination of testes from Cugbp1(-/-) males showed an arrest of spermatogenesis that occurred at step 7 of spermiogenesis, before spermatid elongation begins, and an increased apoptosis. A quantitative reverse transcriptase PCR analysis showed a decrease of all the germ cell markers tested but not of Sertoli and Leydig markers, suggesting a general decrease in germ cell number. In wild-type testes, CUG-BP1 is expressed in germ cells from spermatogonia to round spermatids and also in Sertoli and Leydig cells. These findings demonstrate that CUG-BP1 is required for completion of spermatogenesis.
Kress
Chantal
C
URA 2578 CNRS Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Gautier-Courteille
Carole
C
Osborne
H Beverley
HB
Babinet
Charles
C
Paillard
Luc
L
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D000067879:CELF1 Protein; D002470:Cell Survival; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000166:cytology; D004822:Epididymis / Q000002:abnormalities / Q000166:cytology / Q000196:embryology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005838:Genotype; D005854:Germ Cells / Q000166:cytology; D006130:Growth Disorders / Q000151:congenital*; D007248:Infertility, Male; D008297:Male; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000002:abnormalities / Q000166:cytology / Q000196:embryology
D015415:Biomarkers; D000067879:CELF1 Protein; C502743:CELF1 protein, mouse; D050505:Mutant Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins