The Gas7 gene encodes two protein isoforms differentially expressed within the brain

Gas7, a growth arrest-specific gene first isolated from serum-starved NIH3T3 cells, is expressed abundantly in the brain and is essential for the outgrowth of neurites from cultured cerebellar neurons. Here, we report the existence of a Gas7-related cDNA, designated Gas7-cb, isolated from the mouse cerebellum, and we report the finding that Gas7-cb transcripts and protein are expressed at different locations than those of Gas7. Gas7-cb cDNA differs from the Gas7 cDNA only in the 5' region. Its encoded protein shares the same 320 amino acids in its C-terminus with those of Gas7. Analyses of the RNA and protein expression of Gas7-cb and Gas7 by RNase protection assay and Western blot indicated that while Gas7 expression is predominant in the cerebrum and in growth-arrested NIH3T3 fibroblasts, Gas7-cb expression is predominant in the cerebellum. Characterization of Gas7 and Gas7-cb RNAs and of the genomic structure of murine Gas7 cloned in a bacterial artificial chromosome indicated that the Gas7 gene spans more than 60 kb and consists of at least 15 exons. The 5'-terminus of Gas7-cb is located at exon 6a, which is absent in Gas7 transcripts but is retained in its entirety in Gas7-cb transcripts, resulting in the presence of a unique 20-amino-acid sequence at the N-terminus of the Gas7-cb protein. Our results show that the Gas7 gene encodes two Gas7 isoforms, Gas7 and Gas7-cb, whose expression is differentially regulated within mouse brain.