Levin M L, Chatterjee A, Pragliola A, Worley K C, Wehnert M, Zhuchenko O, Smith R F, Lee C C, Herman G E
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Genome Res. 1996 Jun;6(6):465-77. doi: 10.1101/gr.6.6.465.
The X-linked developmental mouse mutations bare patches (Bpa) and striated (Str) may be homologous to human X-linked dominant chondrodysplasia punctata (CDPX2) and incontinentia pigmenti (IP2), respectively, based on their genetic mapping and clinical phenotypes. Bpa and Str have been localized to an overlapping critical region of 600 kb that demonstrates conserved gene order with loci in human Xq28 between DXS1104 and DXS52. As part of efforts to isolate the genes involved in these disorders, we have begun to develop a comparative transcription map spanning this region in both species. Using techniques of cross-species conservation and hybridization, exon trapping, and cDNA selection we have identified four known genes or members of gene families--caltractin, a member of the gamma-aminobutyric acid (GABAA) receptor gene family, a member of the melanoma antigen gene (MAGE) family, and several members of the murine-specific, X-linked lymphocyte regulated gene (Xlr3) family. Trapped exons and, in some cases, longer cDNAs have been isolated for potentially 7-9 additional genes. One cDNA demonstrates highly significant homology with members of the Krüppel family of zinc finger transcription factors. A second novel cDNA demonstrates homology at the 3' end of the predicted amino acid sequence to a LIM domain consensus. Gene order appears conserved among those cDNAs determined to be present in both human and mouse. Three of the murine transcripts appear to be present in multiple copies within the Bpa/Str critical region and could be associated with a predisposition to genomic rearrangements. Reverse transcriptase PCR (RT-PCR) and Northern analysis 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.
基于基因定位和临床表型，X连锁发育性小鼠突变裸斑（Bpa）和条纹（Str）可能分别与人X连锁显性点状软骨发育不良（CDPX2）和色素失禁症（IP2）同源。Bpa和Str已定位到一个600 kb的重叠关键区域，该区域显示出与人类Xq28中DXS1104和DXS52之间位点保守的基因顺序。作为分离这些疾病相关基因工作的一部分，我们已开始构建跨越两个物种该区域的比较转录图谱。利用跨物种保守性和杂交技术、外显子捕获及cDNA筛选，我们已鉴定出四个已知基因或基因家族成员——钙牵蛋白、γ-氨基丁酸（GABAA）受体基因家族成员、黑色素瘤抗原基因（MAGE）家族成员以及小鼠特异性X连锁淋巴细胞调节基因（Xlr3）家族的几个成员。已分离出捕获的外显子，在某些情况下还分离出了更长的cDNA，用于另外7 - 9个潜在基因。一个cDNA与锌指转录因子Krüppel家族成员具有高度显著的同源性。另一个新的cDNA在预测氨基酸序列的3'端与LIM结构域共有序列具有同源性。在确定同时存在于人和小鼠中的那些cDNA中，基因顺序似乎是保守的。三个小鼠转录本似乎在Bpa/Str关键区域内以多拷贝形式存在，可能与基因组重排的易感性有关。逆转录酶PCR（RT-PCR）和Northern分析表明，其中几个转录本在妊娠中期小鼠胚胎和新生皮肤中表达，这使它们成为Bpa和Str突变及其各自同源人类疾病的候选基因。
