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Identification of possible quantitative trait loci responsible for hyperglycaemia after 70% pancreatectomy using a spontaneously diabetogenic rat

Published online by Cambridge University Press:  01 February 1999

T. OGINO ,
D. H. MORALEJO ,
M. ZHU ,
K. TOIDE ,
S. WEI ,
K. WEI ,
T. YAMADA ,
A. MIZUNO ,
K. MATSUMOTO  and
K. SHIMA
T. OGINO
Affiliation:
Institute for Animal Experimentation, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan Department of Laboratory Medicine, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
D. H. MORALEJO
Affiliation:
Institute for Animal Experimentation, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
M. ZHU
Affiliation:
Department of Laboratory Medicine, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
K. TOIDE
Affiliation:
Department of Laboratory Medicine, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
S. WEI
Affiliation:
Institute for Animal Experimentation, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
K. WEI
Affiliation:
Institute for Animal Experimentation, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
T. YAMADA
Affiliation:
Institute for Animal Experimentation, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
A. MIZUNO
Affiliation:
Department of Laboratory Medicine, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
K. MATSUMOTO
Affiliation:
Institute for Animal Experimentation, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
K. SHIMA
Affiliation:
Department of Laboratory Medicine, University of Tokushima School of Medicine, Kuramoto 3, Tokushima 770, Japan
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Abstract

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The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat exhibits sustained hyperglycaemia after partial pancreatectomy, while the normal control rat does not. This difference is thought to be genetically determined and to be caused by impairment of β-cell regrowth, a possible event involved in the pathogenesis of NIDDM. Our investigation was designed to identify quantitative trait loci (QTL) responsible for post-pancreatectomy hyperglycaemia by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and Fischer-344 (F344) rats. We have identified three possible QTL on rat chromosomes (Chrs) 3, 14 and 19 that account for a total of approximately 75% of the genetic variance in the F2. For the QTL on Chr 14, the OLETF allele corresponds with increased glucose levels, as expected. Surprisingly, for the QTL on Chr 19, the F344 allele corresponds with increased glucose levels. The Chr 3 QTL exhibits heterosis, heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) between the QTL on Chrs 14 and 19.

Type
Research Article
Information
Genetics Research , Volume 73 , Issue 1 , February 1999 , pp. 29 - 36
Copyright
© 1999 Cambridge University Press