PMID- 10331425
OWN - NLM
STAT- MEDLINE
DCOM- 19990527
LR  - 20220330
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 48
IP  - 5
DP  - 1999 May
TI  - Genetic analysis of late-onset type 2 diabetes in a mouse model of human complex 
      trait.
PG  - 1168-74
AB  - Type 2 diabetes is a complex trait with both genes and environmental factors
      contributing to susceptibility. Except for rare subtypes with monogenic
      inheritance, the genetic basis of type 2 diabetes is unknown because of the
      complex and heterogeneous nature of the disease. By using the NSY mouse, an
      inbred mouse model of type 2 diabetes, we genetically dissected late-onset type 2
      diabetes and demonstrated age-dependent changes in the genetic control of type 2 
      diabetes as well as polygenic inheritance. Three major loci (Nidd1nsy, Nidd2nsy, 
      Nidd3nsy) were mapped on mouse chromosomes (Chr) 11, 14, and 6, respectively. The
      existence of a fourth locus (Nidd4nsy) with an age-dependent effect was suggested
      by longitudinal, but not cross-sectional, analysis of linkage data. Nidd1nsy and 
      Nidd4nsy appear to affect insulin secretion, whereas Nidd2nsy and Nidd3nsy appear
      to affect insulin sensitivity. A locus on Chr 6 was significantly linked to
      epididymal fat weight. A candidate disease gene (Tcf2) on Chr 11, encoding
      hepatic nuclear factor-1beta, was shown to have a rare sequence variant in the
      DNA binding domain in the model. The mouse model we used will serve as a useful
      model for future studies on the etiology of late-onset polygenic type 2 diabetes 
      in humans.
FAU - Ueda, H
AU  - Ueda H
AD  - Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
FAU - Ikegami, H
AU  - Ikegami H
FAU - Kawaguchi, Y
AU  - Kawaguchi Y
FAU - Fujisawa, T
AU  - Fujisawa T
FAU - Yamato, E
AU  - Yamato E
FAU - Shibata, M
AU  - Shibata M
FAU - Ogihara, T
AU  - Ogihara T
LA  - eng
SI  - GENBANK/AB008174
SI  - GENBANK/AB008175
SI  - GENBANK/AB008176
SI  - GENBANK/AB008177
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HNF1B protein, human)
RN  - 0 (Hnf1b protein, mouse)
RN  - 0 (Insulin)
RN  - 0 (Transcription Factors)
RN  - 138674-15-4 (Hepatocyte Nuclear Factor 1-beta)
SB  - IM
MH  - Adipose Tissue/anatomy & histology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Chromosome Mapping
MH  - DNA-Binding Proteins/genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - *Disease Models, Animal
MH  - Epididymis
MH  - Female
MH  - Hepatocyte Nuclear Factor 1-beta
MH  - Humans
MH  - Insulin/metabolism/pharmacology
MH  - Insulin Resistance/genetics
MH  - Insulin Secretion
MH  - Longitudinal Studies
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Molecular Sequence Data
MH  - Organ Size
MH  - Transcription Factors/genetics
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
AID - 10.2337/diabetes.48.5.1168 [doi]
PST - ppublish
SO  - Diabetes. 1999 May;48(5):1168-74. doi: 10.2337/diabetes.48.5.1168.