cDNA sequence and chromosomal localization of mouse Dlgh3 gene adjacent tothe BRCA1 tumor suppressor locus

Membrane associated guanylate kinase homologues (MAGUKs) function in tumor suppression and receptor clustering pathways presumably by modulating signa ling events at the interface of the membrane cytoskeleton. The p55 subclass of MAGUKs includes two novel cDNAs that were originally identified by virt ue of their genomic location to human chromosome 17q12-21 where the BRCA1 t umor suppressor gene has been mapped. The predicted primary structure of th e human MPP3 contains a single copy of the PDZ domain, an SH3 motif, and a carboxy-terminal guanylate kinase-like domain. Here we report the full-leng th coding cDNA sequence of the mouse homologue of MPP3. The translated amin o acid sequence of murine Dlgh3 contains 568 amino acids that show 87% sequ ence identity with the human MPP3 protein. Northern blot analysis shows abu ndant expression of a similar to 3.0 kb transcript of Dlgh3 in mouse brain and skeletal muscle, and a relatively less abundant similar to 5.0 kb trans cript in skeletal muscle, testis, kidney, and lung. Using an interspecific backcross panel, the Dlgh3 gene was mapped to a segment of mouse chromosome 11 that is conserved with human chromosome 17q12-21. The close proximity o f murine Dlgh3 gene to the BRCA1 locus and the high conservation of the pri mary structure of human and murine proteins provide a framework for testing the role of Dlgh3 in cell proliferation pathways using the mouse as a mode l system, (C) 1998 Elsevier Science B.V. All rights reserved.