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Molecular and Cellular Biology, May 2002, p. 3066-3077, Vol. 22, No. 9
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.9.3066-3077.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

SH2-B Is Required for Both Male and Female Reproduction

Satoshi Ohtsuka,1 Satoshi Takaki,2 Masanori Iseki,2 Kanta Miyoshi,3 Naomi Nakagata,4 Yuki Kataoka,5 Nobuaki Yoshida,5 Kiyoshi Takatsu,2 and Akihiko Yoshimura1,3*

Division of Molecular Genetics, Institute of Life Science, Kurume University, Kurume 839-0861,1 Division of Immunology, Department of Microbiology and Immunology,2 Laboratory of Gene Expression and Regulation, Center for Experimental Medicine, Institute of Medical Science, The University of Tokyo, Minato-ku 108-8639,5 Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582,3 Division of Reproductive Engineering, Center for Animal Resources & Development, Kumamoto University, Kumamoto 860-0811, Japan4

Received 2 October 2001/ Returned for modification 6 November 2001/ Accepted 7 February 2002

Many growth factors and hormones modulate the reproductive status in mammals. Among these, insulin and insulin-like growth factor I (IGF-I) regulate the development of gonadal tissues. SH2-B has been shown to interact with insulin and IGF-I receptors, although the role of SH2-B in these signals has not been clarified. To investigate the role of SH2-B, we generated mice with a targeted disruption of the SH2-B gene. Both male and female SH2-B-/- mice showed slight retardation in growth and impaired fertility. Female knockout mice possess small, anovulatory ovaries with reduced numbers of follicles and male SH2-B-/- mice have small testes with a reduced number of sperm. SH2-B-/- cumulus cells do not respond to either follicle-stimulating hormone or IGF-I. These data suggest that SH2-B plays a critical role in the IGF-I-mediated reproductive pathway in mice.

* Corresponding author. Mailing address: Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-6822. Fax: 81-92-642-6825. E-mail: yakihiko{at}bioreg.kyushu-u.ac.jp.

Molecular and Cellular Biology, May 2002, p. 3066-3077, Vol. 22, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.9.3066-3077.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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