PHENOTYPIC CONSEQUENCES OF IMPRINTING PERTURBATIONS AT RASGRF1 IN MOUSE

Rasgrf1 is imprinted and paternally-expressed in neonatal mouse brain. At weaning, expression becomes biallelic. Manipulating the elements regulating imprinted Rasgrf1 expression produces mice with transient perturbations in Rasgrf1 imprinting, which we can use to assay the consequences of aberrant imprinting during a specific developmental time. As neonates, monoallelic-paternal (wild-type) mice paternally express Rasgrf1; biallelic mice express Rasgrf1 from both alleles; null mice do not express Rasgrf1; and monoallelic-maternal mice reciprocally express Rasgrf1, from the maternal allele. This last genotype represents a unique opportunity to study the effects of expression derived from either of the two parental alleles. All genotypes biallelically express Rasgrf1 around weaning. Two phenotypes appear when Rasgrf1 imprinted is perturbed: a difference in size, and a difference in performance on an associative odor-learning task at postnatal day 8 (P8). Size differences persist through adulthood and reflect the level of Rasgrf1 expressed pre-weaning: biallelics ar