Identification of two chromosomal loci determining glucose intolerance in a C57BL/6 mouse strain.
OBJECTIVE
Our objective was to map the genes responsible for poor glucose tolerance in a C57BL/6 (B6) mouse model, which provides a human model of non-insulin-dependent diabetes mellitus. Insulin secretion was found to be significantly lower in B6 than in C3H/He (C3H) mice (analysis of variance, P < 0.05) at 10, 20, and 30 minutes during the intraperitoneal glucose tolerance test (IPGTT: 1.5 g glucose/kg of body weight).


METHODS
Mean 30-minute blood glucose values during IPGTT at 8, 9, and 10 weeks of age were used as a surrogate for glucose tolerance. The primers of 87 genetic microsatellite markers (14.9 +/- 6.2 cM apart) genome-wide quantitative trait linkage (QTL) analysis in F2 and F3 mice with the highest and lowest (n = 15 for each extreme) 30-minute blood glucose values were used.


RESULTS
Genome-wide QTL analysis confirmed the locus (D2Mit48) on chromosome 2, with a LOD score of 8.3, and the locus (D13Mit48) on chromosome 13, with a LOD score of 4.2 in F3. Direct sequencing of candidate genes, proprotein convertase-2 (PC2) on chromosome 2 and proprotein convertase-1/3 (PC1/PC3) on chromosome 13, failed to reveal a mutation or polymorphism specific to B6 mice.


CONCLUSIONS
Use of QTL mapping revealed two loci associated with poor glucose tolerance of B6.
Kayo
T
T
Department of Hygiene, Akita University School of Medicine, Japan.
Fujita
H
H
Nozaki
J
J
E
X
X
Koizumi
A
A
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL / Q000235:genetics*; D018895:Microsatellite Repeats
D001786:Blood Glucose; D007328:Insulin