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Evidence for tissue-specific alternative splicing of the ovine insulin receptor gene

  • P.D. McGrattan (a1), A.R.G. Wylie (a1) (a2) and A.J. Bjourson (a1)

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Alternative splicing of a discrete 36 base pair segment (exon 11) of the human and rat insulin receptor leads to the formation of high and low affinity isoforms differing as much as 3-fold in affinity for insulin. Alternative splicing is a common mechanism for generating protein isoforms and is often regulated in a tissue-specific fashion (Seino & Bell, 1989; Mosthaf et al., 1990). In humans, the lower affinity (B-isoform) mRNA transcript is predominantly expressed in tissues that are important for modulating glucose homeostasis such as the liver and muscle whereas the higher affinity (A-isoform) mRNA transcript is predominantly expressed in haematopoietic tissues such as spleen. Alternative splicing of the region of the ovine insulin receptor gene encoding exon 11 has recently been demonstrated (McGrattan et al., unpublished). The objective of the present study was to establish whether tissue-specific regulation of alternative splicing of the insulin receptor gene occurs in the ruminant animal.

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McClain, D.A. (1991) Different ligand affinities of the two human insulin receptor splice variants are reflected in parallel changes in sensitivity for insulin action. Molecular Endocrinology 4: 734739.
McGrattan, P.D., Wylie, A.R.G., Steen, R.J. and Nelson, J. (1997) Tissue specific differences in insulin receptor characteristics in the mature bovine animal. Proceedings of the British Society of Animal Science 51.
Mosthaf, L., Grako, K., Dull, T.J., Coussens, L., Ullrich, A. and McClain, D.A. (1990) Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO Journal 9: 24092413.
Seino, S. and Bell, G.I. (1989) Alternative splicing of the human insulin receptor mRNA. Biochemical and Biophysical Research Communications 159: 312316.
Wylie, A.R.G., McGrattan, P.D. and Nelson, J. (1997): Insulin receptor characteristics in ruminant tissues. Effects of breed, sex and stage of development. 14th Symposium on Energy Metabolism of Farm Animals. Newcastle, Northern Ireland. (in press).

Evidence for tissue-specific alternative splicing of the ovine insulin receptor gene

  • P.D. McGrattan (a1), A.R.G. Wylie (a1) (a2) and A.J. Bjourson (a1)

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