Characterizations of candidate genes for IDD susceptibility from the diabetes-prone NOD mouse strain.
The nucleotide sequences of the NOD and C57BL/6J alleles of Glut-2, Sod-2, and Il-2 were determined by RT-PCR sequencing. Each of these loci is located in intervals that strongly correlated with susceptibility to diabetes in an (NOD/Uf x C57BL/6J)F1 x NOD/Uf backcross. No significant variations in the alleles of Glut-2 at 16 cM on Chromosome (Chr) 3 or Sod-2 at 8 cM on Chr 17 were detected. However, the Il-2 allele in NOD at 20 cM on Chr 3 was found to differ from that in C57BL/6J by a complex mutation involving the contraction of a simple sequence repeat (SSR). Il-2 in NOD differs from the allele in C57BL/6J via a complex mutation involving a deletion of four CAG codons from the SSR together with a length-compensatory four-codon duplication of a segment 5' from the SSR. Two nonsynonymous mutations in the coding region 5' to the SSR were also detected. Only these two allelic forms of Il-2 were detected in a survey of 13 standard inbred lines and 4 wild mouse strains. We propose to designate these alleles as Il-2a (for alleles such as C57BL/6J that contain 12 CAG repeats) and Il-2b (for alleles such as NOD), which occurred in a variety of standard inbred strains and in all four wild Mus musculus domesticus tested. The distribution of these Il-2 alleles among inbred strains correlated with the detection of Chr 3 as an interval effecting diabetes susceptibility in three separate genetic crosses.(ABSTRACT TRUNCATED AT 250 WORDS)
Chesnut
K
K
Center for Mammalian Genetics, College of Medicine University of Florida, Gainesville 32610-0275.
She
J X
JX
Cheng
I
I
Muralidharan
K
K
Wakeland
E K
EK
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004247:DNA; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005091:Exons; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
D004247:DNA