International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

D16 Novel Alternatively Spliced Form of Nbr1 Redefines Brcal - Nbr1 Intergenic Region with Putative Bi-Directional Promoter Conserved in Human and Rodents

Stoil Dimitrov, Maria Brennerova and Jiri Forejt. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20, Prague 4, Czech Republic

Breast and ovarian cancer susceptibility gene (BRCA1) is considered a tumor suppressor gene because loss of heterozygosity or transcriptional downregulation of the gene is associated with cancer. Brca1 is known to lie head-to-head to Nbr1 in mice and to NBR2 in human, transcribed in the opposite directions. The physiological functions of Brca1 and Nbr1 are unclear though the high expression in testes and intimate association of BRCA1 with Rad51 on axial cores of synaptonemal complexes in pachytene cells indicates a possible role of this gene in meiotic recombination. While the coding regions of both genes are conserved in human and mice, the 5' regions and the intergenic region was found to be duplicated in human and to display striking differences in genomic organization and in the cis-control elements of the putative Brca1 - Nbr1 bi-directional promoter.

Here we describe a new, testis specific transcript of the Nbr1 gene in the mouse and rat. The new 1A exon in the 5' region of the gene moves its transcriptional start site closer to the Brca1 transcriptional start site. The newly defined 287 bp distance between both genes corresponds much better to 218 bp human BRCA1 - NBR2 intergenic region. Comparison of steady-state levels of ubiquitous and testis-specific forms of Nbr1 mRNA revealed 20 times higher expression of the testis-specific form in adult testis. The semiquantitative RT PCR was done by reverse transcription of mRNA from developing testes of males between 8 and 32 days old. The expression profiles of the ubiquitous form of Nbr1 and Brca1 were almost identical and differed considerably from the expression profile of the testis-specific form of Nbr1. We will discuss the possible significance of these findings to the organization of the Brca1-Nbr1/BRCA1-NBR2 intergenic region and its putative bi-directional promoter.


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