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Title

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

AuthorsEsteban, Luis Miguel; Núñez, Alejandro; Santos de Dios, Eugenio CSIC ORCID ; Fernández-Medarde, Alberto; Porteros, Ángel; Tessarollo, Lino
Issue DateApr-2002
PublisherAmerican Society for Microbiology
CitationMolecular and Cellular Biology 22(8): 2498–2504 (2002)
AbstractThe 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.
Publisher version (URL)http://dx.doi.org/22.8.2498–2504.2002
URIhttp://hdl.handle.net/10261/5140
DOI10.1128/MCB.22.8.2498-2504.2002
ISSN0270-7306
Appears in Collections:(IBMCC) Artículos

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