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Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-A(y.).

Suto J, Satou K - J. Vet. Med. Sci. (2014)

Bottom Line: The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A(y) males.Using a backcross progeny of DDD × (B6 × DDD.Cg-A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight.The DDD allele was associated with decreased plasma insulin levels.

View Article: PubMed Central - PubMed

Affiliation: Agrogenomics Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8634, Japan.

ABSTRACT
The A(y) allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-A(y) male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-A(y) males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A(y) males. Using a backcross progeny of DDD × (B6 × DDD.Cg-A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-A(y) males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-A(y) and DDD males), individual housing (single DDD.Cg-A(y) male) and single male housing with females (single DDD.Cg-A(y) male with DDD.Cg-A(y) or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-A(y) males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-A(y) males.

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QTL mapping of plasma insulin levels. (A) The genome-wide LOD score plot for plasma insulin levels in BC Ay mice. A horizontal dotted line indicates the genome-wide threshold LOD score for significant linkage. (B) Identification of a significant QTL on distal chromosome 4. Horizontal dotted lines indicate the threshold LOD scores for significant linkage (P<0.05, upper line) and suggestive linkage (P<0.63, lower line). A horizontal short line indicates 95% CI for the QTL.
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fig_005: QTL mapping of plasma insulin levels. (A) The genome-wide LOD score plot for plasma insulin levels in BC Ay mice. A horizontal dotted line indicates the genome-wide threshold LOD score for significant linkage. (B) Identification of a significant QTL on distal chromosome 4. Horizontal dotted lines indicate the threshold LOD scores for significant linkage (P<0.05, upper line) and suggestive linkage (P<0.63, lower line). A horizontal short line indicates 95% CI for the QTL.

Mentions: A histogram showing the distribution of plasma insulin levels in BC Ay mice. The approximate mean insulin values of the parental strains are indicated by arrows.


Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-A(y.).

Suto J, Satou K - J. Vet. Med. Sci. (2014)

QTL mapping of plasma insulin levels. (A) The genome-wide LOD score plot for plasma insulin levels in BC Ay mice. A horizontal dotted line indicates the genome-wide threshold LOD score for significant linkage. (B) Identification of a significant QTL on distal chromosome 4. Horizontal dotted lines indicate the threshold LOD scores for significant linkage (P<0.05, upper line) and suggestive linkage (P<0.63, lower line). A horizontal short line indicates 95% CI for the QTL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363023&req=5

fig_005: QTL mapping of plasma insulin levels. (A) The genome-wide LOD score plot for plasma insulin levels in BC Ay mice. A horizontal dotted line indicates the genome-wide threshold LOD score for significant linkage. (B) Identification of a significant QTL on distal chromosome 4. Horizontal dotted lines indicate the threshold LOD scores for significant linkage (P<0.05, upper line) and suggestive linkage (P<0.63, lower line). A horizontal short line indicates 95% CI for the QTL.
Mentions: A histogram showing the distribution of plasma insulin levels in BC Ay mice. The approximate mean insulin values of the parental strains are indicated by arrows.

Bottom Line: The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A(y) males.Using a backcross progeny of DDD × (B6 × DDD.Cg-A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight.The DDD allele was associated with decreased plasma insulin levels.

View Article: PubMed Central - PubMed

Affiliation: Agrogenomics Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8634, Japan.

ABSTRACT
The A(y) allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-A(y) male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-A(y) males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A(y) males. Using a backcross progeny of DDD × (B6 × DDD.Cg-A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-A(y) males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-A(y) and DDD males), individual housing (single DDD.Cg-A(y) male) and single male housing with females (single DDD.Cg-A(y) male with DDD.Cg-A(y) or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-A(y) males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-A(y) males.

Show MeSH
Related in: MedlinePlus