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Molecular and Cellular Biology, November 2006, p. 8507-8514, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01488-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

CIB1 Is Essential for Mouse Spermatogenesis{triangledown}

Weiping Yuan,1 Tina M. Leisner,1 Andrew W. McFadden,1 Shantres Clark,1 Sylvia Hiller,2 Nobuyo Maeda,2 Deborah A. O'Brien,3,4 and Leslie V. Parise1,4*

Department of Pharmacology,1 Lineberger Comprehensive Cancer Center,4 Pathology and Laboratory Medicine,2 Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 275993

Received 10 August 2006/ Accepted 31 August 2006

CIB1 is a 22-kDa calcium binding, regulatory protein with ~50% homology to calmodulin and calcineurin B. CIB1 is widely expressed and binds to a number of effectors, such as integrin {alpha}IIb, 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.

* Corresponding author. Mailing address: Department of Pharmacology, School of Medicine, CB7365, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Phone: (919) 966-2238. Fax: (919) 966-5640. E-mail: parise{at}med.unc.edu.

{triangledown} Published ahead of print on 18 September 2006.

Molecular and Cellular Biology, November 2006, p. 8507-8514, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01488-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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