Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse.

Abstract

The homozygous and heterozygous phenotypes are described and characterized for 45 new pink-eyed dilution (p) locus mutations, most of them radiation-induced, that affect survival at various stages of mouse development. Cytogenetically detectable aberrations were found in three of the new p mutations (large deletion, inversion, translocation), with band 7C involved in each case. The complementation map developed from the study of 810 types of compound heterozygotes identifies five functional units: jls and jlm (two distinct juvenile-fitness functions, the latter associated with neuromuscular defects), pl-1 and pl-2 (associated with early-postimplantation and preimplantation death, respectively), and nl [neonatal lethality associated with cleft palate (the frequency of rare "escapers" from this defect varied with the genotype)]. Orientation of these units relative to genetic markers is as follows: centromere, Gas-2, pl-1, jls, jlm p, nl (equatable to cp 1 = Gabrb3); pl-2 probably resides in the c-deletion complex. pl-1 does not mask preimplantation lethals between Gas2 and p; and no genes affecting survival are located between p and cp1. The alleles specifying mottling or darker pigment (generically, pm and px, respectively) probably do not represent deletions of p-coding sequences but could be small rearrangements involving proximal regulatory elements.

Molecular analysis of 36 mutations at the mouse pink-eyed dilution (p) locus.

“…Twenty-nine of 33 mutations tested (three not tested) showed deletion of all fragments recognized by DN10. One pF', pZnFi0', is not deleted for any plocus probes tested but has been shown to be a large paracentric inversion (RUSSELL et al 1995).…”

“…Mice: Induction and recovery of plocus mutations are described in the accom anying report (RUSSELL et al 1995). One mutation (pl7MNZ1%), included in this study but not in the companion study, was induced in spermatogonial stem cells by methylnitrosourea at a dose of 75 mg/kg.…”

“…1995). The derivation of compound heterozygotes that carry complementing mutations is described elsewhere (CULIAT et al 1993;RUSSELL et al 1995). Molecular probes and Southern blotting: Seventeen molecular probes were employed in Southern blot analysis to assay for deletions or other types of rearrangements among pregion mutations and to provide data for the construction of a map of the overlap among deletions.…”

“…The human HPWGA locus, which encodes a protein that interacts with the E6 oncogene of human papilloma virus and the p53 tumor suppressor protein, maps to human 1591 1-913 between GABRB3 and SNRPN (NA- KAO et al 1994). Among 13 deletions that include Gahb3, and thus extend distally from p, a M. musculus specific RFLV at the Hpveba locus was found to be deleted in only p3up"6, a deletion that also extends proximally from p to include l(7)lRl (RUSSELL et al 1995). 2 and 3.…”

“…The accompanying report (RUSSELL et al 1995) summarizes the origin, method of induction, and initial genetic analyses of 45 Oak Ridge plocus mutations. Most of these were radiation-induced, and they include 38 p, five p" ("dark pink-eyed"), and two p" (mottled) mutations.…”