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Molecular and Cellular Biology, April 2002, p. 2498-2504, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2498-2504.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Targeted Disruption of Ras-Grf2 Shows Its Dispensability for Mouse Growth and Development

Alberto Fernández-Medarde,1 Luis M. Esteban,1 Alejandro Núñez,1 Ángel Porteros,2 Lino Tessarollo,3 and Eugenio Santos1*

Centro de Investigación del Cáncer, IBMCC, CSIC-USAL,1 Departamento de Biología Celular y Patología, University of Salamanca, 37007 Salamanca, Spain,2 Mammalian Genetics Laboratory, National Cancer Institute, Frederick, Maryland 217023

Received 29 May 2001/ Returned for modification 31 July 2001/ Accepted 15 January 2002

The mammalian Grf1 and Grf2 proteins are Ras guanine nucleotide exchange factors (GEFs) sharing a high degree of structural homology, as well as an elevated expression level in central nervous system tissues. Such similarities raise questions concerning the specificity and/or redundancy at the functional level between the two Grf proteins. grf1-null mutant mice have been recently described which showed phenotypic growth reduction and long-term memory loss. To gain insight into the in vivo function of Grf2, we disrupted its catalytic CDC25-H domain by means of gene targeting. Breeding among grf2+/- animals gave rise to viable grf2-/- adult animals with a normal Mendelian pattern, suggesting that Grf2 is not essential for embryonic and adult mouse development. In contrast to Grf1-null mice, analysis of grf2-/- litters showed similar size and weight as their heterozygous or wild-type grf2 counterparts. Furthermore, adult grf2-/- animals reached sexual maturity at the same age as their wild-type littermates and showed similar fertility levels. No specific pathology was observed in adult Grf2-null animals, and histopathological studies showed no observable differences between null mutant and wild-type Grf2 mice. These results indicate that grf2 is dispensable for mouse growth, development, and fertility. Furthermore, analysis of double grf1/grf2 null animals did not show any observable phenotypic difference with single grf1-/- animals, further indicating a lack of functional overlapping between the two otherwise highly homologous Grf1 and Grf2 proteins.

* 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: esantos{at}usal.es.

Molecular and Cellular Biology, April 2002, p. 2498-2504, Vol. 22, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.8.2498-2504.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ruiz, S., Santos, E., Bustelo, X. R. (2007). RasGRF2, a Guanosine Nucleotide Exchange Factor for Ras GTPases, Participates in T-Cell Signaling Responses. Mol. Cell. Biol. 27: 8127-8142 [Abstract] [Full Text]  
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