International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

Dr Steven Joseph Clapcott
University of Oxford
Department of Zoology
South Parks Road
Oxford
OX1 3PS
UK

Co-Authors:  Peter J, Graham CF
Institution:   Medical Research Council

Two new alleles of rasgrf1 induced by enu mutagenesis

We report the identification of two new alleles of Rasgrf1, induced by random mutagenesis with ENU. Two lines of mice originating from different founder males, GENA37 and GENA53, were found to have restricted post natal growth. This phenotype was dominant and heritable only via the male line. Genetic mapping revealed linkage of the restricted growth phenotype to a region of chromosome 9 containing the paternally-expressed gene, Rasgrf1. cDNA sequencing of heterozygous mice of both lines showed that GENA53 and GENA37 had point mutations in Rasgrf1 inducing stop signals at codons 608 and 1106, respectively. No Ras-GRF1 protein has been detected in whole brain.  Null mutations of Rasgrf1 have been produced previously with Neo placements.  These KO lines also have restricted growth, as well as impaired learning and memory.  However, one KO line is reported to have impaired amygdala-dependent long-term memory whilst another has an impairment in hippocampal-dependent learning and memory. Studies are currently under way to analyse the learning and memory characteristics of GENA37 and GENA53, and thus clarify the role of Ras-GRF1 in cognition.