Two ENU-induced mutations in Rasgrf1 and early mouse growth retardation.

When paternally transmitted, two independent ENU-induced mutations showed reduced whole body wet weight soon after birth. The mutations were mapped to Chromosome 9 (Chr 9) between the markers D9Mit208 and D9Mit215. Their map position and imprinted status suggested that they might alter RAS protein-specific guanine nucleotide releasing factor 1 expression. Both mutations introduced premature chain termination codons into the coding sequence of Rasgrf1, and no Ras-GRF1 protein was detected in the brain. The GENA53 line had a C to T transition at nucleotide 2137, and the line GENA37 had a T to A transversion at nucleotide 3552 of the cDNA sequence. Mutant mice had near normal body weight at birth, but their weight started to lag behind that of wild-type littermates during the first week, and they were about 15% lighter as adults.