A COMPARATIVE TRANSCRIPTION MAP OF THE MURINE BARE PATCHES (BPA) AND STRIATED (STR) CRITICAL REGIONS AND HUMAN XQ28

The X-linked developmental mouse mutations bare patches (Bpa) and stri ated (Str) may be homologous to human X-linked dominant chondrodysplas ia punctata (CDPX2) and incontinentia pigmenti (IP2), respectively, ba sed on their genetic mapping and clinical phenotypes. Bpa and Str have been Localized to an overlapping critical region of 600 kb that demon strates conserved gene order with loci in human Xq28 between DXS1104 a nd DXS52. As part of efforts to isolate the genes involved in these di sorders, we have begun to develop a comparative transcription map span ning this region in both species. Using techniques of cross-species co nservation and hybridization, exon trapping, and cDNA selection we hav e identified four known genes or members of gene families-caltractin, a member of the gamma-aminobutyric acid (GABA(A)) receptor gene family , a member of the melanoma antigen gene (MAGE) family, and several mem bers of the murine-specific, X-linked lymphocyte regulated gene (Xlr3) family. Trapped exons and, in some cases, longer cDNAs have been isol ated for potentially 7-9 additional genes. One cDNA demonstrates highl y significant homology with members of the Kruppel family of zinc fing er transcription factors. A second novel cDNA demonstrates homology at the 3' end of the predicted amino acid sequence to a LIM domain conse nsus. Gene order appears conserved among those cDNAs determined to be present in both human and mouse. Three of the murine transcripts appea r to be present in multiple copies within the Bpa/Str critical region and could be associated with a predisposition to genomic rearrangement s. Reverse trancriptase PCR (RT-PCR) and Northern analyses demonstrate that several of the transcripts are expressed in mid-gestation murine embryos and neonatal skin, making them candidates for the Bpa and Str mutations and their respective homologous human disorders.