<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>Fetuin/α<sub>2</sub>-HS glycoprotein (α<sub>2</sub>-HSG) homologs have been identified in several species including rat, sheep, pig, rabbit, guinea pig, cattle, mouse and human. Multiple physiological roles for these homologs have been suggested, including ability to bind to hydroxyapatite crystals and to specifically inhibit the tyrosine kinase (TK) activity of the insulin receptor (IR). In this study we report the identification, cloning, and characterization of the mouse Ahsg gene and its function as an IR-TK inhibitor. Genomic clones derived from a mouse Svj 129 genomic library were sequenced in order to characterize the intron–exon organization of the mouse Ahsg gene, including an 875 bp subclone containing 154 bp upstream from the transcription start site, the first exon, and part of the first intron. A second genomic subclone harboring a 3.45 kb Bgl II fragment contained exons 2, 3 and 4 in addition to two adjacent elements within the first intron-a repetitive element of the B1 family (92 bp) and a 271 bp tract of (T,C)<italic>n</italic> * (A,G)<italic>n</italic>. We have mapped mouse Ahsg at 16 cM adjacent to the Diacylglycerol kinase 3 (Dagk3) gene on chromosome 16 by genotyping interspecific backcross panels between C57BL/6J and <italic>Mus spretus</italic>. The position is syntenic with human chromosome 3q27, where the human AHSG gene resides. Using recombinant mouse α<sub>2</sub>-HSG expressed from a recombinant baculovirus,
we demonstrate that mouse α<sub>2</sub>-HSG inhibits insulin–stimulated IR autophosphorylation and
IR-TKA <italic>in vitro</italic>. In addition, mouse α<sub>2</sub>-HSG (25μg/ml) completely abolishes insulin-induced
DNA synthesis in H-35 rat hepatoma cells. Based on
the sequence data and functional analysis, we conclude
that the mouse Ahsg gene is the true ortholog
of the human AHSG gene.</p>
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Int J Exp Diabetes Res. 2000; 1(4):249-263