A novel model of obesity-related diabetes: introgression of the Lepr(fa) allele of the Zucker fatty rat into nonobese Spontaneously Diabetic Torii (SDT) rats.

An fa allele of the leptin receptor gene (Lepr(fa)) of the Zucker fatty rat was introduced into the genome of the Spontaneously Diabetic Torii (SDT) rat, an inbred model of nonobese type 2 diabetes mellitus, through the 'Speed congenic method'. The newly established congenic strain of a SDT rat for Lepr(fa) was maintained by intercrossing between fa-heterozygous littermates, and the phenotypes related to obesity and diabetes were investigated till 32 wks of age. SDT fa/fa rats of both sexes exhibited obesity, adiposity and insulin resistance associated with hyperphagia from the loss of leptin action. Interestingly, they developed diabetes from 5 wks of age in males and 8 wks in females with the incidences reaching 100% at 16 wks in males and 73% at 32 wks in females. In contrast, heterozygous (+/fa) and wild-type (+/+) rats developed spontaneous nonobese diabetes in males from approximately 20 wks, but not in females, as with the original SDT rats. These results indicate that the fa gene accelerates the onset of diabetes in SDT rats by making adiposity and/or insulin resistance as potent risk factors for development of their diabetes. The SDT.Lepr(fa) congenic rat strain is expected to be a novel model of obesity-related diabetes and could be a useful tool for studies of the genetic backgrounds of diabetes in response to fa-induced obesity.     

Ontogeny of GTP-binding proteins,Gi and G0, in rat retina

The distribution and the levels of G_i1 (plus G_i3), G_i2, and G₀ in rat retina were studied immunohistochemically and immunochemically during development. At embryonic day (E) 15, G_i1α/G_i3α was observed in the inner layer of the neural retina, the future nerve fiber layer (NFL), while G_i2α was observed both in the inner and outer layers of the neural retina. No immunoreactivity for G₀α was observed. At E18, G_i1α/G_i3α and G_i2α appeared in the inner plexiform layer (IPL), while G₀α was faintly immunoreactive only in the NFL. At birth, G_i2α/G_i3α and G₀α appeared in the ganglion cell layer. G_i2α was intensely immunoreactive in the NFL and IPL. At postnatal day (P) 10, the inner portions of the retina, from the NFL to the outer plexiform layer, were immunoreactive to G_i1α/G_i3α, G_i2α, and G₀α. G_i1α/G_i3α and G₀α were distributed characteristically in a laminated pattern in the IPL, but G_i2α was present homogeneously in the IPL. At P12, G_i2α appeared in the outer nuclear layer. As the postnatal days advanced, the laminated pattern of immunoreactivity to G₀α in the IPL became diffuse, but immunoreactivity to G_i1α/G_i3α remained. The results of enzyme immunoassays showed that the concentration of G₀α increased rapidly from P10 to P15 and reached almost the adult level at P20–P30, while G_i2α decreased until P15 and was almost constant thereafter. These results showed that the distribution of G_i1α/G_i3α, G_i2α, and G₀α differs during development, suggesting that each G protein in the developing retina has a unique function.