CIB1 is essential for mouse spermatogenesis.
CIB1 is a 22-kDa calcium binding, regulatory protein with approximately 50% homology to calmodulin and calcineurin B. CIB1 is widely expressed and binds to a number of effectors, such as integrin alphaIIb, PAK1, and polo-like kinases, in different tissues. However, the in vivo functions of CIB1 are not well understood. To elucidate the function of CIB1 in whole animals, we used homologous recombination in embryonic stem cells to generate Cib1(-/-) mice. Although Cib1(-/-) mice grow normally, the males are sterile due to disruption of the haploid phase of spermatogenesis. This is associated with reduced testis size and numbers of germ cells in seminiferous tubules, increased germ cell apoptosis, and the loss of elongated spermatids and sperm. Cib1(-/-) testes also show increased mRNA and protein expression of the cell cycle regulator Cdc2/Cdk1. In addition, mouse embryonic fibroblasts (MEFs) derived from Cib1(-/-) mice exhibit a much slower growth rate compared to Cib1(+/+) MEFs, suggesting that CIB1 regulates the cell cycle, differentiation of spermatogenic germ cells, and/or differentiation of supporting Sertoli cells.
Yuan
Weiping
W
Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Leisner
Tina M
TM
McFadden
Andrew W
AW
Clark
Shantres
S
Hiller
Sylvia
S
Maeda
Nobuyo
N
O'Brien
Deborah A
DA
Parise
Leslie V
LV
D019342:Acetic Acid / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology*; D049109:Cell Proliferation; D004822:Epididymis / Q000473:pathology; D005347:Fibroblasts / Q000502:physiology; D005557:Formaldehyde / Q000737:chemistry; D007248:Infertility, Male / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010851:Picrates / Q000737:chemistry; D011995:Recombination, Genetic; D013087:Spermatids / Q000502:physiology; D013090:Spermatocytes / Q000502:physiology; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism* / Q000473:pathology
D002135:Calcium-Binding Proteins; C491605:Cib1 protein, mouse; D010851:Picrates; D005557:Formaldehyde; C026239:Bouin's solution; D016203:CDC2 Protein Kinase; D019342:Acetic Acid