Physical analysis of murine albino deletions that disrupt liver-specific gene regulation or mesoderm development

Abstract

Complementation analyses of radiation-induced deletion mutations involving the albino (c) locus in Chromosome (Chr) 7 of the mouse have identified several loci, in addition to c, that have important roles in development. The "mesoderm-deficient" (msd) and "hepatocyte-specific developmental regulation-1" (hsdr-1) loci, which are proximal and tightly linked to c, are important in the formation of mesoderm and in the regulation of liver- and kidney-specific induction of various enzymes and proteins, respectively. Cloning deletion-breakpoint-fusion fragments caused by lethal albino deletions that genetically define the extents of the msd and hsdr-1 loci is one way of generating molecular probes for studying the gene(s) involved in these phenotypes. The distal breakpoints of five such deletions were positioned on a long-range (PFGE) map of approximately 1.7 Mb of wild-type DNA surrounding the c, D7Was12, and Emv-23 loci. In addition, the distal breakpoints of two viable albino deletions, which remove part of the tyrosinase gene and extend distally, were localized in the vicinity of the lethal deletion breakpoints. Therefore, the viable deletions can be exploited to generate additional DNA probes that should facilitate the isolation of breakpoint clones from chromosomes carrying lethal deletions defining hsdr-1 and msd.