Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain.
Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using marker-assisted speed congenic protocols, enforced by selective removal of other QTL regions (QTL-marker-assisted counterselection), to efficiently transfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into the OLETF background. In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. We conclude that single-allele correction of an impaired genetic pathway can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.
Okuno
S
S
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
Watanabe
T K
TK
Ono
T
T
Oga
K
K
Mizoguchi-Miyakita
A
A
Yamasaki
Y
Y
Goto
Y
Y
Shinomiya
H
H
Momota
H
H
Miyao
H
H
Hayashi
I
I
Asai
T
T
Suzuki
M
M
Harada
Y
Y
Hishigaki
H
H
Wakitani
S
S
Takagi
T
T
Nakamura
Y
Y
Tanigami
A
A
D000483:Alleles; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006943:Hyperglycemia / Q000235:genetics*; D006949:Hyperlipidemias / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D011922:Rats, Mutant Strains
D001786:Blood Glucose; D005819:Genetic Markers