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cDNA sequence and chromosomal localization of mouse Dlgh3 gene adjacent to the BRCA1 tumor suppressor locus
L Lin1, L L Peters, S L Ciciotte
1Laboratory of Tumor Cell Biology, St. Elizabeth's Medical Center, Tufts University School of Medicine, ACH4, 736 Cambridge Street, Boston, MA 02135, USA.
Abstract:
Membrane associated guanylate kinase homologues (MAGUKs) function in tumor suppression and receptor clustering pathways presumably by modulating signaling events at the interface of the membrane cytoskeleton. The p55 subclass of MAGUKs includes two novel cDNAs that were originally identified by virtue of their genomic location to human chromosome 17q12-21 where the BRCA1 tumor suppressor gene has been mapped. The predicted primary structure of the 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-length coding cDNA sequence of the mouse homologue of MPP3. The translated amino acid sequence of murine Dlgh3 contains 568 amino acids that show 87% sequence identity with the human MPP3 protein. Northern blot analysis shows abundant expression of a approximately 3.0 kb transcript of Dlgh3 in mouse brain and skeletal muscle, and a relatively less abundant approximately 5.0 kb transcript 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 of murine Dlgh3 gene to the BRCA1 locus and the high conservation of the primary structure of human and murine proteins provide a framework for testing the role of Dlgh3 in cell proliferation pathways using the mouse as a model system.
Insights
Researchers identified the mouse homologue of human MPP3, named Dlgh3. This gene is expressed in various mouse tissues and mapped to a chromosome segment conserved with human chromosome 17, near the BRCA1 tumor suppressor gene.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Membrane-associated guanylate kinase homologues (MAGUKs) are implicated in tumor suppression and receptor clustering.
- The p55 subclass of MAGUKs includes novel cDNAs located near the BRCA1 tumor suppressor gene on human chromosome 17q12-21.
- Human MPP3, a p55 MAGUK, possesses PDZ, SH3, and guanylate kinase-like domains.
Purpose of the Study:
- To report the full-length coding cDNA sequence of the mouse homologue of human MPP3.
- To characterize the expression pattern and chromosomal location of the mouse Dlgh3 gene.
- To establish a framework for studying Dlgh3's role in cell proliferation using a mouse model.
Main Methods:
- Sequencing of the full-length coding cDNA for mouse MPP3 homologue (Dlgh3).
- Northern blot analysis to determine Dlgh3 transcript expression levels in various mouse tissues.
- Interspecific backcross panel analysis to map the Dlgh3 gene on the mouse genome.
Main Results:
- The translated amino acid sequence of murine Dlgh3 shows 87% identity with human MPP3.
- Dlgh3 exhibits abundant expression in mouse brain and skeletal muscle, with less abundant transcripts in other tissues.
- The Dlgh3 gene was mapped to mouse chromosome 11, a region conserved with human chromosome 17q12-21.
Conclusions:
- The high sequence conservation and conserved chromosomal location of Dlgh3 suggest a potential role in pathways related to the BRCA1 locus.
- The mouse Dlgh3 provides a valuable model system for investigating the function of p55 MAGUKs in cell proliferation and tumor suppression.
- Further studies on Dlgh3 are warranted to elucidate its involvement in cancer and other cellular processes.