Molecular Analyses of MHC Genes and T Cell Receptor V.BETA. Gene Usage in the NOD Mouse and Its Nondiabetic Sister Strains.

Abstract

It is generally held that one of the recessive genes controlling diabetes in the NOD mouse is linked to the major histocompatibility complex (MHC) . We therefore performed restriction fragment length polymorphism studies of MHC (class I, II, and III) in NOD mice in comparison with those of their nondiabetic sister strains, NON, CTS, and ILI mice which were derived from the same Jcl-ICR mice. When a minimum of four restriction enzymes were used, class II and III genes of NOD mice were indistinguishable from those of CTS and ILI mice but totally different from those of NON mice. While NON mice expressed the Eα gene, NOD, CTS, and ILI mice appeared to carry a deletion in the 5' end of the Eα gene resulting in failure to transcribe the Eα gene. When class I probe was used, CTS mice showed very different band patterns from those of the other ICR-derived mice.Unique substitution of Asp57 with Ser in the Aβ chain is considered to make the Aβ gene the MHC-linked susceptibility gene. We therefore analyzed the nucleotide sequences of the Aβ second exon in ILI, CTS, and NON mice. The DNA sequence analyses revealed that the Aβ second exon sequences in the ILI and CTS mice, but not in the NON mouse, are identical to that of the NOD mouse. Taken together, these data suggest that ILI and CTS mice possess a recessive diabetogenic gene linked to the MHC.We also examined the difference of Vβ usage between the NOD mouse and the ILI mouse spleen cells. No obvious difference, however, was evident.