Abnormal sperm in mice with targeted deletion of the act (activator of cAMP-responsive element modulator in testis) gene.
ACT [activator of cAMP-responsive element modulator (CREM) in testis] is a LIM-only protein that interacts with transcription factor CREM in postmeiotic male germ cells and enhances CREM-dependent transcription. CREM regulates many crucial genes required for spermatid maturation, and targeted mutation of the Crem gene in the mouse germ-line blocks spermatogenesis. Here we report the phenotype of mice in which targeted disruption of the act gene was obtained by homologous recombination. Whereas the seminiferous tubules of the act(-/-) mice contain all of the developmental stages of germ cells and the mice are fertile, the amount of mature sperm in the epididymis is drastically reduced. The residual sperm display severe abnormalities, including fully folded tails and aberrant head shapes. These results indicate that numerous postmeiotic genes under CREM control require the coactivator function of ACT. Thus, the fine-tuning of sperm development is achieved by the coordinated action of two transcriptional regulators.
Kotaja
Noora
N
Institut de Génétique et de Biologie Moléculaire et Cellulaire, B.P. 10142, 67404 Illkirch-Strasbourg, France.
De Cesare
Dario
D
Macho
Betina
B
Monaco
Lucia
L
Brancorsini
Stefano
S
Goossens
Ellen
E
Tournaye
Herman
H
Gansmuller
Anne
A
Sassone-Corsi
Paolo
P
D000818:Animals; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D016547:Kinesins / Q000378:metabolism; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins; D013081:Sperm Motility; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000002:abnormalities* / Q000378:metabolism / Q000648:ultrastructure; D013737:Testis / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C504657:Fhl5 protein, mouse; C409642:KIF17 protein, mouse; D060588:LIM Domain Proteins; D020409:Molecular Motor Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator; D016547:Kinesins