| First Author | Fernández-Medarde A | Year | 2002 |
| Journal | Mol Cell Biol | Volume | 22 |
| Issue | 8 | Pages | 2498-504 |
| PubMed ID | 11909944 | Mgi Jnum | J:75928 |
| Mgi Id | MGI:2178054 | Doi | 10.1128/MCB.22.8.2498-2504.2002 |
| Citation | Fernandez-Medarde A, et al. (2002) Targeted disruption of Ras-Grf2 shows its dispensability for mouse growth and development. Mol Cell Biol 22(8):2498-504 |
| abstractText | 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. |
