Identification of a human LRMX1 (LMX1.1)-related gene, LMX1.2: Tissue-specific expression and linkage mapping on chromosome 9

LMX1 is a LIM-homeodomain (LIM-HD)-containing protein expressed selectively in insulin-producing beta-cell lines, and it it has been shown to activate insulin gene transcription. The human LMX1 gene was mapped by fluorescence in situ hybridization to chromosome region 1q22-q23, yet Church et al. (1994, Nat. Genet. 6: 98-105) identified two exon-trapping products from human chromosome 9 that were highly homologous to hamster LMX1. In the current study, we demonstrate tissue-specific expression of an LMX1 (now known as LMX1.1)-related gene, named LMX1.2. The chicken C-LMX1 gene, recently cloned using the hamster LMX1.1 sequence and shown to specify dorsal cell fate during vertebrate limb development (9), is actually more related to human LMX1.1 than LMX1.1. We have identified a unique simple sequence repeat polymorphic marker (hLMX1.2CA1) in a P1 genomic clone containing the human LMX1.2 gene and genetically mapped the marker on chromosome 9 between markers D9S1825 and D9S290 with odds of at least 1000:1. In addition, we localized the human LMX1.1 gene to three CEPH "B" yeast artificial chromosome clones (907A11, 935B12, and 947B2), along with two nearby polymorphic markers (D1S426 and D1S194)). Identification of this new LIM-HD-related gene may provide the opportunity to elucidate further the function of LIM class homeobox genes. Nearby polymorphic markers will be useful in testing the hypothesis that mutations in these LIM-HD genes result in genetic diseases such as non-insulin-dependent diabetes mellitus. (C) 1997 Academic Press.