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Molecular and Cellular Biology, September 2000, p. 6410-6413, Vol. 20, No. 17
0270-7306/00/$04.00+0

Ras-Guanine Nucleotide Exchange Factor Sos2 Is Dispensable for Mouse Growth and Development

Luis M. Esteban,1,2 Alberto Fernández-Medarde,1,2 Eva López,2 Kate Yienger,2 Carmen Guerrero,1,2 Jerrold M. Ward,3 Lino Tessarollo,4 and Eugenio Santos1,2,*

Centro de Investigación del Cáncer, IBMCC, CSIC-USAL, University of Salamanca, 37007 Salamanca, Spain1; Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 208922; and Veterinary and Tumor Pathology Section3 and Mammalian Genetics Laboratory,4 National Cancer Institute, Frederick, Maryland 21702

Received 21 April 2000/Accepted 22 May 2000

The mammalian sos1 and sos2 genes encode highly homologous members of the Son-of-sevenless family of guanine nucleotide exchange factors. They are ubiquitously expressed and play key roles in transmission of signals initiated by surface protein tyrosine kinases that are transduced into the cell through the action of membrane-associated Ras proteins. Recent reports showed that targeted disruption of the sos1 locus results in embryonic lethality. To gain insight into the in vivo function of sos2, we disrupted its catalytic CDC25-H domain by means of gene targeting techniques. Mating among heterozygous sos2+/- mice produced viable sos2-/- offspring with a normal Mendelian pattern of inheritance, indicating that the loss of sos2 does not interfere with embryo viability in the uterus. Adult homozygous mutant sos2-/- mice reached sexual maturity at the same age as their wild-type littermates, and both male and female null mutants were fertile. Histopathological analysis showed no observable differences between mutant and wild-type mice. Our results show that unlike the case for sos1, sos2 gene function is dispensable for normal mouse development, growth, and fertility.

* Corresponding author. Mailing address: Centro de Investigación del Cáncer, IBMCC, USAL-CSIC, Campus Unamuno, University of Salamanca, 37007 Salamanca, Spain. Phone: 34 923 294720. Fax: 34 923 294743. E-mail: cicancer{at}usal.es.

Molecular and Cellular Biology, September 2000, p. 6410-6413, Vol. 20, No. 17
0270-7306/00/$04.00+0


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