RGD Reference Report - Identification of novel non-insulin-dependent diabetes mellitus susceptibility loci in the Otsuka Long-Evans Tokushima fatty rat by MQM-mapping method. - Rat Genome Database

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Identification of novel non-insulin-dependent diabetes mellitus susceptibility loci in the Otsuka Long-Evans Tokushima fatty rat by MQM-mapping method.

Authors: Sugiura, K  Miyake, T  Taniguchi, Y  Yamada, T  Moralejo, DH  Wei, S  Wei, K  Sasaki, Y  Matsumoto, K 
Citation: Sugiura K, etal., Mamm Genome 1999 Dec;10(12):1126-31.
RGD ID: 69696
Pubmed: PMID:10594234   (View Abstract at PubMed)

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, non-insulin-dependent diabetes mellitus (NIDDM) in humans. We have previously identified 11 quantitative trait loci (QTLs) responsible for NIDDM susceptibility on Chromosomes (Chrs) 1, 5, 7, 8, 9, 11, 12, 14, and 16 (Nidd1-11/of for Non-insulin-dependent diabetes 1-11/oletf) by using the interval mapping method in 160 F(2) progenies obtained by mating the OLETF and the Fischer-344 (F344) rats. MQM-mapping, which was applied for QTL analysis based on multiple-QTL models, is reported to be more powerful than interval mapping, because in the process of mapping one QTL the genetic background, which contains the other QTLs, is controlled. Application of MQM-mapping in the F(2) intercrosses has led to a revelation of three novel QTLs on rat Chrs 5 (Nidd12/of), 7 (Nidd13/of), and 17 (Nidd14/of), in addition to Nidd1-11/of loci. The three QTLs, together with the Nidd1-11/of, account for a total of approximately 70% and approximately 85% of the genetic variance of the fasting and postprandial glucose levels, respectively, in the F(2). While the OLETF allele corresponds with increased glucose levels as expected for Nidd12 and 14/of, the Nidd13/of exhibits heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. There is epistatic interaction between Nidd2 and 14/of. Additionally, our results indicated that the novel QTLs could show no linkage with body weight, but Nidd12/of has an interaction with body weight.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IDA 69696; 69696; 69696; 69696; 69696; 69696; 69696; 69696; 69696 RGD 
type 2 diabetes mellitus  IAGP 69696 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
impaired glucose tolerance  QTM 69696; 69696; 69696; 69696; 69696; 69696; 69696; 69696; 69696; 69696; 69696 RGD 
impaired glucose tolerance  IAGP 69696; 69696 RGD 
Objects Annotated

QTLs
Niddm19  (Non-insulin dependent diabetes mellitus QTL 19)
Niddm20  (Non-insulin dependent diabetes mellitus QTL 20)
Niddm22  (Non-insulin dependent diabetes mellitus QTL 22)
Niddm23  (Non-insulin dependent diabetes mellitus QTL 23)
Niddm24  (Non-insulin dependent diabetes mellitus QTL 24)
Niddm25  (Non-insulin dependent diabetes mellitus QTL 25)
Niddm26  (Non-insulin dependent diabetes mellitus QTL 26)
Niddm27  (Non-insulin dependent diabetes mellitus QTL 27)
Niddm28  (Non-insulin dependent diabetes mellitus QTL 28)
Niddm29  (Non-insulin dependent diabetes mellitus QTL 29)
Niddm30  (Non-insulin dependent diabetes mellitus QTL 30)
Niddm31  (Non-insulin dependent diabetes mellitus QTL 31)
Niddm32  (Non-insulin dependent diabetes mellitus QTL 32)

Strains
F344/DuCrlCrlj  (NA)
OLETF/Got  (Otsuka Long Evans Tokushima)

Objects referenced in this article
Strain F344.OLETF-(D17Mgh4-Edn1)/Tj null Rattus norvegicus
Strain F344.OLETF-(D5Mgh29-D5Mgh22)/Tj null Rattus norvegicus
Strain F344.OLETF-(D7Rat31-D7Rat35)/Tj null Rattus norvegicus

Additional Information