Inbred animals with inherited susceptibility to disease can be especially informative regarding pathogenetic mechanisms because they carry naturally occurring genetic variants of the same type that cause disease in humans. This principle is illustrated by Rosengren et al., whose analysis of an inbred strain of rats prone to develop type 2 diabetes led to the discovery of a gene whose aberrant overexpression suppresses pancreatic insulin secretion in both rats and humans. The culprit gene, ADRA2A, encodes the alpha2A adrenergic receptor and is potentially a valuable lead for diabetes therapy because it can be targeted pharmacologically.
A. H. Rosengren, R. Jokubka, D. Tojjar, C. Granhall, O. Hansson, D.-Q. Li, V. Nagaraj, T. M. Reinbothe, J. Tuncel, L. Eliasson, L. Groop, P. Rorsman, A. Salehi, V. Lyssenko, H. Luthman, E. Renström, Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes. Science 327, 217–220 (2010). [Abstract] [Full Text]