A GENE ESSENTIAL TO BRAIN GROWTH AND DEVELOPMENT MAPS TO THE DISTAL ARM OF RAT-CHROMOSOME-12

A recently discovered, spontaneous, autosomal recessive mutation in ra ts, flathead (fh), results in greatly reduced brain growth beginning i n late fetal development. In this study we have mapped the fh mutation by determining the pattern of segregation of polymorphic microsatelli te markers with respect to fh in 51 affected F-2 offspring from a sing le interstrain intercross. Two markers on chromosome 12, D12Rat80 and D12Mgh6, cosegregated with the fh mutation in all 51 affected animals. The distribution of six additional markers in 40 informative meioses further localizes fh approximately 2 cM teleomeric to nos1. There are no known mutations in homologous regions of either mouse or human geno mes that result in deficits in late neurodevelopment similar to that o bserved in fh/fh animals. The unique phenotype of fh/fh animals and th e location of fh suggests the presence of a novel gene essential to no rmal brain development on the distal end of rat chromosome 12. (C) 199 8 Elsevier Science Ireland Ltd. All rights reserved.