Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity

Kim, Jung Han; Stewart, Taryn P.; Zhang, Weidong; Kim, Hyoung Yon; Nishina, Patsy M.; Naggert, Jürgen Κ.

doi:10.1152/physiolgenomics.00197.2004

Cited by 48 publications

(38 citation statements)

References 72 publications

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“…For example, Bwq2 [24] and Tabw2 [8] apparently overlap with Bwdq2 and Obdq1 on chromosome 6. We previously identified Bwq2 as a modifier QTL for the A y allele in an F 2 intercross between B6 and obese KK-A y strains [23,24].…”

Section: Discussionmentioning

confidence: 99%

Quantitative Trait Loci that Control Body Weight and Obesity in an F2 Intercross between C57BL/6J and DDD.Cg-Ay Mice

Suto

2011

The Journal of Veterinary Medical Science

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Section: Discussionmentioning

confidence: 99%

Quantitative Trait Loci that Control Body Weight and Obesity in an F2 Intercross between C57BL/6J and DDD.Cg-Ay Mice

Suto

2011

The Journal of Veterinary Medical Science

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“…TallyHo mice represent a newly defined polygenetic model of Type II diabetes and are characterized by hyperglycemia, hyperinsulinemia, hyperlipidemia, and moderate obesity (23,24,52). It has been suggested that TallyHo mice may be more representative of the polygenic nature of Type II diabetes in humans (23).…”

mentioning

confidence: 99%

Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes

Didion¹,

Lynch²,

Faraci³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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.-The purpose of this study was to characterize vascular responses and to examine mechanisms of vascular dysfunction in TallyHo mice, a new polygenic model of Type II diabetes. Responses of cerebral arterioles and carotid arteries were examined in vivo by using a cranial window and in vitro by using tissue baths, respectively. Dilatation of cerebral arterioles (baseline diameter ϭ 33 Ϯ 1 m) in response to acetylcholine, but not to nitroprusside, was markedly reduced (P Ͻ 0.05) in TallyHo mice. Responses of cerebral arterioles to acetylcholine in TallyHo mice were restored to normal with polyethylene glycol-superoxide dismutase (100 U/ml; a superoxide scavenger). Responses to acetylcholine were also greatly impaired (P Ͻ 0.05) in the carotid arteries from TallyHo mice. Phenylephrine-and serotonin-, but not to KCl-or U46619-, induced contraction was increased two-to fourfold (P Ͻ 0.05) in carotid arteries of TallyHo mice. Responses to phenylephrine and serotonin were reduced to similar levels in the presence of Y-27632 (an inhibitor of Rho kinase; 3 mol/l). These findings provide the first evidence that vascular dysfunction is present in TallyHo mice and that oxidative stress and enhanced activity of Rho kinase may contribute to altered vascular function in this genetic model of Type II diabetes. carotid artery; cerebral circulation; endothelium; microcirculation EPIDEMIOLOGICAL STUDIES suggest that there is a marked increase in the number of vascular complications in patients with diabetes (21,22,51). For example, results from the Framingham study have found a two-to fourfold increased risk associated with diabetes and the development of other cardiovascular risk factors, including atherosclerosis, carotid artery disease, and stroke (21). Although Type II diabetes accounts for the majority (ϳ90%) of diabetes in humans (3), relatively little is known regarding vascular responses and mechanisms that produce vascular dysfunction in Type II diabetes compared with Type I diabetes.Whereas studies using ob/ob (leptin-deficient) and db/db (leptin receptor-deficient mice) have provided much insight into vascular alterations in the genetic models of Type II diabetes (8,19,25,42,(43)(44)(45)(46), such monogenic deficiencies in leptin and the leptin receptor are rare and are not always associated with the development of diabetes in humans (14). TallyHo mice represent a newly defined polygenetic model of Type II diabetes and are characterized by hyperglycemia, hyperinsulinemia, hyperlipidemia, and moderate obesity (23,

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“…With respect to QTLs for leptin in obese mice, Kim et al [10] reported a similar result. A congenic mouse strain B6.TH-tabw2/tabw2, which carries obesity QTL tabw2 from the obese TallyHo mouse strain, had increased plasma leptin concentrations compared with control B6.TH-+/+ mice.…”

Section: Females (N=298) C) Reference Map Position (Cm) Was Retrievementioning

confidence: 74%

QTL Mapping of Genes Controlling Plasma Insulin and Leptin Concentrations: Metabolic Effect of Obesity QTLs Identified in an F2 Intercross between C57BL/6J and DDD.Cg-Ay Inbred Mice

Suto

2013

The Journal of Veterinary Medical Science

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ABSTRACT. DDD.Cg-A y female mice developed massive obesity as compared with B6.Cg-A y female mice. We previously identified quantitative trait loci (QTLs) for obesity on chromosomes 1, 6, 9 and 17 in F 2 female mice, including F 2 A y (F 2 mice with the A y allele) and F 2 non-A y mice (F 2 mice without the A y allele), produced by crossing C57BL/6J and DDD.Cg-A y strains. We here addressed the question whether the obesity QTLs share genetic bases with putative QTLs for plasma glucose, insulin and leptin concentrations. We performed QTL analyses for the first principal component (PC1) extracted from these metabolic measurements to identify the genes that contributed to the comprehensive evaluation of metabolic traits. By single QTL scans, we identified two significant QTLs for insulin concentration on chromosomes 6 and 12, three for leptin concentration on chromosomes 1, 6 and 17, and five for PC1 on chromosomes 1, 6, 12 (two loci) and 17. Although insulin and leptin concentrations and PC1 were not normally distributed in combined F 2 mice, results of single QTL scans by parametric and non-parametric methods were very similar. Therefore, QTL scan by the parametric method was performed with the agouti locus genotype as a covariate. A significant QTL × covariate interaction was found for PC1 on chromosome 9. All obesity QTLs had significant metabolic effects. Thus, obesity-and diabetes-related traits in DDD.Cg-A y mice were largely controlled by QTLs on chromosomes 1, 6, 9, 12 and 17.

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Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity

Cited by 48 publications

References 72 publications

Quantitative Trait Loci that Control Body Weight and Obesity in an F2 Intercross between C57BL/6J and DDD.Cg-Ay Mice

Quantitative Trait Loci that Control Body Weight and Obesity in an F2 Intercross between C57BL/6J and DDD.Cg-Ay Mice

Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes

QTL Mapping of Genes Controlling Plasma Insulin and Leptin Concentrations: Metabolic Effect of Obesity QTLs Identified in an F<sub>2</sub> Intercross between C57BL/6J and DDD.Cg-<i>A<sup>y</sup></i> Inbred Mice

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