MOLECULAR-GENETICS OF THE BROWN (B)-LOCUS REGION OF MOUSE CHROMOSOME-4 .2. COMPLEMENTATION ANALYSES OF LETHAL BROWN DELETIONS

Numerous new mutations at the brown (b) locus in mouse chromosome 4 ha ve been recovered over the years in germ-cell mutagenesis experiments performed at the Oak Ridge National Laboratory. A large series of radi ation- and chemical-induced b mutations known to be chromosomal deleti ons, and also known to be prenatally lethal when homozygous, were anal yzed by pairwise complementation crosses as well as by pseudodominance tests involving flanking loci defined by externally visible phenotype s. These crosses were designed to determine the extent of each deletio n on the genetic and phenotype map of the chromosomal region surroundi ng the b locus; the crosses also provided basic data that assigned del etions to complementation groups and defined four new loci associated with aberrancies in normal development. Specifically, the pseudodomina nce tests identified deletions that include the proximally mapping whi rler (wi) and the distally mapping depilated (dep) genes, thereby brac keting these loci defined by visible developmental abnormalities with landmarks (deletion breakpoints) that are easily identified on the phy sical map. Furthermore, the complementation crosses, which were supple mented with additional crosses that allowed determination of the gross time of lethality of selected deletions, defined four new loci requir ed for normal development. Homozygous deletion of one of these loci (b -associated fitness, baf) results in a runting syndrome evident during postnatal development; deletion of one locus [l(4)2Rn] causes death i n the late gestation/neonatal period; and deletion of either of two lo ci [l(4)1Rn or 1(4)3Rn] results in embryonic death, most likely in pre -, peri- or postimplantation stages. The placement of these new functi onally defined loci on the evolving molecular map of the b region shou ld be useful for continuing the analysis of the roles played in develo pment by genes in this segment of chromosome 4.