The SMXA: a new set of recombinant inbred strain of mice consisting of 26 substrains and their genetic profile

Nishimura, Masahiko; Hirayama, Nobuyuki; Serikawa, Tadao; Kanehira, Kazunori; Matsushima, Yoshibumi; Katoh, Hideki; Wakana, Shigeharu; Kojima, Akinori; Hayashi, Hiroshi

doi:10.1007/bf00292434

Cited by 50 publications

(32 citation statements)

References 39 publications

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“…The SMXA-5 mouse is one of the 26 SMXA recombinant inbred (RI) substrains that have been established from parental strains SM/J and A/J [17]. Each SMXA RI strain has a mosaic genome derived from the SM/J and A/J strains.…”

Section: Introductionmentioning

confidence: 99%

Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains

Kobayashi

Kawai

et al. 2006

Diabetologia

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Aims/hypothesis: The SMXA-5 mouse is one of the SMXA recombinant inbred substrains established from the non-diabetic SM/J and A/J strains, and is a model for polygenic type 2 diabetes, characterised by moderately impaired glucose tolerance and hyperinsulinaemia. These diabetic traits are worsened by feeding a high-fat diet. The aim of this study was to dissect the diabetogenic loci in the A/J regions of the SMXA-5 genome that contribute to diabetes-related traits. Materials and methods: We analysed the quantitative trait loci (QTL) for diabetes-related traits and obesity in (SM/J×SMXA-5)F 2 intercross mice fed a high-fat diet. To verify the function of the responsible locus that was mapped in the present study, we constructed a congenic strain and characterised its diabetes-related traits. Results: A major QTL for glucose tolerance, free-fed blood glucose concentration and BMI was mapped on chromosome 2. This locus existed near D2Mit15, with the highest logarithm of the odds score (12.6) for glucose concentration at 120 min in a glucose tolerance test, and was designated T2dm2sa. The diabetogenic allele of T2dm2sa originated in the A/J strain. SM.A-T2dm2sa, a congenic strain that introgressed the T2dm2sa region of A/J genome into SM/J, exhibited overt impaired glucose tolerance and hyperinsulinaemia. Conclusions/interpretation: The development of impaired glucose tolerance in SM.A-T2dm2sa mice confirmed the results of QTL analysis for diabetes-related traits in F 2 intercross mice. The present results suggest that there are latent diabetogenic loci in the genomes of non-diabetic A/J and SM/J mice, and that the coexistence of these loci, including T2dm2sa, causes impaired glucose tolerance in SMXA-5 and SM.A-T2dm2sa mice.

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Section: Introductionmentioning

confidence: 99%

Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains

Kobayashi

Kawai

et al. 2006

Diabetologia

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“…RI strains are a powerful tool for analyzing not only single genetic traits but also multifactorial genetic traits. Nishimura et al (16) constructed a novel set of 26 SMXA RI mouse strains from SM/J and A/J strains. The parental strains (SM/J and A/J) possess differences in a variety of phenotypic traits (16,17).…”

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confidence: 99%

“…Nishimura et al (16) constructed a novel set of 26 SMXA RI mouse strains from SM/J and A/J strains. The parental strains (SM/J and A/J) possess differences in a variety of phenotypic traits (16,17). In particular, genetic analyses for pulmonary adenoma (18) and body weight (19) were performed using the SMXA RI strains, and these QTLs have already been mapped.…”

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confidence: 99%

Combinations of Nondiabetic Parental Genomes Elicit Impaired Glucose Tolerance in Mouse SMXA Recombinant Inbred Strains

et al. 2003

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Type 2 diabetes in humans is not a single gene disorder but a multifactorial disease caused by the interaction of multiple genes and environmental factors. Recombinant inbred (RI) strains are a powerful tool for analyzing not only single genetic traits but also multifactorial genetic traits. By using the SMXA RI mice, we genetically dissected diabetes-related traits (BMI, nonfasting blood glucose concentration, and blood glucose concentration during intraperitoneal glucose tolerance tests). For minimizing the variation of glucose tolerance in each strain, all mice were fed the high-carbohydrate diet and subjected to phenotypic and genetic analyses. The parental strains, SM/J and A/J, were nondiabetic, and the differences of the mean values of diabetes-related traits were small. In contrast, an impaired glucose tolerance was observed in (SM ؋ A)F1 mice, and marked differences in diabetes-related traits were observed in 19 SMXA RI strains. In particular, several SMXA RI strains showed markedly impaired glucose tolerance and hyperglycemia. Quantitative trait locus (QTL) analysis revealed a locus on chromosome (Chr) 10 contributing significant effect on nonfasting blood glucose concentration, as well as six diabetes-related loci on four chromosomes with suggestive evidence of linkage with diabetes-related phenotypes. The A/J-derived QTLs on Chr 2 and 18 and an SM/J-derived QTL on Chr 10 contributed to the impairment of glucose tolerance and/or the increase of blood glucose concentration. The present study indicates that QTLs derived from parental SM/J and A/J genomes, both of which are nondiabetic, interact in the RI genomes, leading to the development of hyperglycemia and diabetic phenotypes. Genetic dissection of this kind of diabetogenesis will increase our understanding of the complex gene-gene interaction and mode of inheritance in human type 2 diabetes.

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“…The SMXA recombinant inbred (RI) strains are derived from the systematic inbreeding of randomly selected pairs of F 2 offspring produced by crossing female SM/J and male A/J mice [16]. The SMXA RI strains have been used for the genetic analysis of polygenic traits.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Trait Locus Analysis of Serum Insulin, Triglyceride, Total Cholesterol and Phospholipid Levels in the (SM/J*A/J)F2 Mice.

et al. 2003

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The SMXA: a new set of recombinant inbred strain of mice consisting of 26 substrains and their genetic profile

Cited by 50 publications

References 39 publications

Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains

Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains

Combinations of Nondiabetic Parental Genomes Elicit Impaired Glucose Tolerance in Mouse SMXA Recombinant Inbred Strains

Quantitative Trait Locus Analysis of Serum Insulin, Triglyceride, Total Cholesterol and Phospholipid Levels in the (SM/J*A/J)F2 Mice.

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