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

Anunciado, Rea Victoria P.; Nishimura, Masahiko; Mori, Masayuki; Ishikawa, Akira; Tanaka, Shin; Horio, Fumihiko; Ohno, Tamio; Namikawa, Takao

doi:10.1538/expanim.52.37

Cited by 22 publications

(10 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is suggested that the gene commonly contributing to obesity may exist in the centromeric region of chromosome 12. However, there is no QTL for obesity on chromosome 12 in the studies using SMXA RI substrains or (SM×A)F 2 mice [19,48,49]. Therefore, this QTL may be a locus specifically activated under a high-fat diet.…”

Section: Discussionmentioning

confidence: 98%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 98%

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

View full text Add to dashboard Cite

show abstract

“…Anunciado et al (22)(23)(24) have mapped a series of traits, including some mapped here, in RI lines and an F 2 intercross between SM/J and A/J mouse strains. Since this cross shares a parent with the cross reported here, it is possible that some of the same QTLs may be discovered in both studies.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Trait Loci for Obesity- and Diabetes-Related Traits and Their Dietary Responses to High-Fat Feeding in LGXSM Recombinant Inbred Mouse Strains

et al. 2004

View full text Add to dashboard Cite

Genetic variation in response to high-fat diets is important in understanding the recent secular trends that have led to increases in obesity and type 2 diabetes. The examination of quantitative trait loci (QTLs) for both obesity-and diabetes-related traits and their responses to a high-fat diet can be effectively addressed in mouse model systems, including LGXSM recombinant inbred (RI) mouse strains. A wide range of obesity-and diabetes-related traits were measured in animals from 16 RI strains with 8 animals of each sex fed a high-or low-fat diet from each strain. Marker associations were measured at 506 microsatellite markers spread throughout the mouse genome using a nested ANOVA. Locations with significant effects on the traits themselves and/or trait dietary responses were identified after correction for multiple comparisons by limiting the false detection rate. Nonsyntenic associations of marker genotypes were common at QTL locations so that the significant results were limited to loci still significant in multiple QTL models. We discovered 91 QTLs at 39 locations. Many of these locations (n ‫؍‬ 31) also showed genetic effects on dietary response, typically because the loci produced significantly larger effects on the high-fat diet. Fat depot weights, leptin levels, and body weight at necropsy tended to map to the same locations and were responsible for a majority of the dietary response QTLs. Basal glucose levels and the response to glucose challenge mapped together in locations distinct from those affecting obesity. These QTL locations form a panel for further research and fine mapping of loci affecting obesity-and diabetes-related traits and their responses to high-fat feeding. Diabetes 53: 3328 -3336, 2004 T he prevalence of obesity and its correlates, such as type 2 diabetes, has increased greatly over the last 20 years (1). There has also been a concomitant change in the age of onset for type 2 diabetes, with increasing diagnoses of this disease in children, adolescents, and young adults (2). These secular changes in obesity and diabetes are not due to genetic changes in populations (3), rather they are due to environmental changes in nutrition and activity over time. Even so, there is genetic variation in humans in the response to dietary and activity factors. Some individuals respond strongly to an obesogenic environment by becoming obese, while other individuals remain lean when challenged by the same environment (4). These variations in response to environmental stimuli are, in part, due to genetic variations between people.Study of differential response to dietary factors in human populations can be challenging because of the difficulty in controlling or accurately recording diet over an extended period of time. Animal studies of the genetic basis for differential response to dietary factors can play an important role in attempts to understand the genetics involved in recent increases in obesity and type 2 diabetes. We have used the cross of inbred mouse strains LG/J and SM/J over the past y...

show abstract

“…Shike et al [18] and the K allele was associated with increased T-CHO levels. Anunciado et al [1] identified T-CHO QTL near D3Mit46 (13.8 cM) in SM/J × A/J F 2 . This chromosome 3 locus had effects on PL and T-CHO, but not on TG, the same as the effect of Cq3.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Cq3, a Quantitative Trait Locus that Controls Plasma Cholesterol and Phospholipid Levels in Mice

Suto

2006

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. Cq3 was identified in C57BL/6J (B6) × KK-A y F 2 mice as a quantitative trait locus (QTL) that controls plasma cholesterol and phospholipid levels, and normolipidemic B6 allele was associated with increased lipids. Cq3 was statistically significant in F 2 -a/a, but not in F 2 -A y /a; probably because the Cq3 effect was obscured by introduction of the A y allele, which in itself has a strong hyperlipidemic effect. Because the peak LOD score for Cq3 was identified near D3Mit102 (49.7 cM) on chromosome 3, linkage analyses with microsatellite markers located at 49.7 cM were performed in KK × RR F 2 , B6 × RR F 2 , and KK × CF1 F 2 . However, even a suggestive QTL was not identified in any of the three F 2 . By testing all pairs of marker loci, I found a significant interaction between Cq3 and the Apoa2 locus, and F 2 mice with the Apoa2 KK /Apoa2 KK ; D3Mit102 B6 /D3Mit102 B6 genotype had significantly higher cholesterol levels than did F 2 mice with other genotypes. The results showed that the 'round-robin' strategy was not always applicable to the search for QTL genes; probably because specific gene-to-gene interaction limited the validity of the strategy to the utmost extent.

show abstract

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

Cited by 22 publications

References 19 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

Quantitative Trait Loci for Obesity- and Diabetes-Related Traits and Their Dietary Responses to High-Fat Feeding in LGXSM Recombinant Inbred Mouse Strains

Characterization of Cq3, a Quantitative Trait Locus that Controls Plasma Cholesterol and Phospholipid Levels in Mice

Contact Info

Product

Resources

About