DEFECTIVE FOREBRAIN DEVELOPMENT IN MUTANT MICE

Ernest Gallo Clinic And Research Center, Emeryville CA

Investigators

Abstract

DESCRIPTION: The ultimate objective of this work is to understand the role that the otocephaly (oto) and flat-top (flat) loci play in the development of the forebrain. The X-irradiation induced oto mutation was isolated at the Jackson Lab in a screen for lethal loci on chromosome 1. Homozygous oto mice lack a lower jaw and lack many or all forebrain structures, but otherwise appear normal. The specificity of the defects withing the CNS suggests that deciphering the role of the too gene will uncover pivotal aspects of forebrain patterning. The flat mutation was generated by the investigator in a screen for ENU-induced mutations that disrupt early forebrain development. The telencephalic vesicles, first detectable between 9 and 10 days of gestation, are the early progenitors of the cerebral cortex and basal ganglia. In homozygous flat embryos the telecephalic vesicles do not form. The objectives are to determine the developmental and genetic bases of the defects in the nervous system of these two mutations. We will accomplish these goals by analyzing in detail the development of mutant embryos and by mapping the genes that determine the phenotypes. Defects in forebrain development will be studied by analyzing the expression of marker genes in mutant embryos at a variety of developmental time points. The genetics of the phenotype will be studied by using linkage analysis to map the mutations.