1. Mamm Genome. 1998 Jun;9(6):419-25.
Genetic dissection of "OLETF", a rat model for non-insulin-dependent diabetes
mellitus.
Kanemoto N(1), Hishigaki H, Miyakita A, Oga K, Okuno S, Tsuji A, Takagi T,
Takahashi E, Nakamura Y, Watanabe TK.
Author information:
(1)Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10,
Kagasuno, Kawauchi-cho, Tokushima 771-01, Japan.
To elucidate the genetic factors underlying non-insulin-dependent diabetes
mellitus (NIDDM), we performed genome-wide quantitative trait locus (QTL)
analysis, using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat
is an excellent animal model of NIDDM because the features of the disease closely
resemble human NIDDM. Genetic dissection with two kinds of F2 intercross progeny,
from matings between the OLETF rat and non-diabetic control rats F344 or BN,
allowed us to identify on Chromosome (Chr) 1 a major QTL associated with features
of NIDDM that was common to both crosses. We also mapped two additional
significant loci, on Chrs 7 and 14, in the (OLETF x F344)F2 cross alone, and
designated these three loci as Diabetes mellitus, OLETF type Dmo 1, Dmo2 and Dmo3
respectively. With regard to suggestive QTLs, we found loci on Chrs 10, 11, and
16 that were common to both crosses, as well as loci on Chrs 5 and 12 in the
(OLETF x F344)F2 cross and on Chrs 4 and 13 in the (OLETF x BN)F2 cross. Our
results showed that NIDDM in the OLETF rat is polygenic and demonstrated that
different genetic backgrounds could affect "fitness" for QTLs and produce
different phenotypic effects from the same locus.
PMID: 9585427 [PubMed - indexed for MEDLINE]
PUBMED: 9585427
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