Genetic variance and covariance patterns for body weight and energy 
balance characters in an advanced intercross population of mice

Leamy, Larry J.; Elo, Kari; Nielsen, Marie Vejrup; Vleck, L.D. Van; Pomp, Daniel

doi:10.1051/gse:2004042

Cited by 10 publications

(29 citation statements)

References 26 publications

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“…Heart weight is heritable in both mice and humans, with narrow-sense heritability ( h 2) for mouse heart weight estimated between 0.07 and 0.59 (Deschepper et al 2002; Leamy et al 2005; Philip et al 2011). Human genome-wide association studies (GWAS) have associated multiple loci with cardiac mass using non-invasive metrics such as echocardiography and electrocardiography (Vasan et al 2009; Shah et al 2011; Fox et al 2013; Wild et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Quantitative trait mapping in Diversity Outbred mice identifies two genomic regions associated with heart size

et al. 2017

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Heart size is an important factor in cardiac health and disease. In particular, increased heart weight is predictive of adverse cardiovascular outcomes in multiple large community-based studies. We use two cohorts of Diversity Outbred (DO) mice to investigate the role of genetics, sex, age, and diet on heart size. DO mice (n = 289) of both sexes from generation 10 were fed a standard chow diet, and analyzed at 12-15 weeks of age. Another cohort of female DO mice (n = 258) from generation 11 were fed either a high-fat, cholesterol-containing (HFC) diet or a low-fat, high-protein diet, and analyzed at 24-25 weeks. We did not observe an effect of diet on body or heart weight in generation 11 mice, although we previously reported an effect on other cardiovascular risk factors, including cholesterol, triglycerides, and insulin. We do observe a significant genetic effect on heart weight in this population. We identified two quantitative trait loci for heart weight, one (Hwtf1) at a genome-wide significance level of p ≤ 0.05 on MMU15 and one (Hwtf2) at a genome-wide suggestive level of p ≤ 0.1 on MMU10, that together explain 13.3% of the phenotypic variance. Hwtf1 contained collagen type XXII alpha 1 chain (Col22a1), and the NZO/HlLtJ and WSB/EiJ haplotypes were associated with larger hearts. This is consistent with heart tissue Col22a1 expression in DO founders and SNP patterns within Hwtf1 for Col22a1. Col22a1 has been previously associated with cardiac fibrosis in mice, suggesting that Col22a1 may be involved in pathological cardiac hypertrophy.

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Section: Introductionmentioning

confidence: 99%

Quantitative trait mapping in Diversity Outbred mice identifies two genomic regions associated with heart size

et al. 2017

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“…In terms of direct estimates the majority of the data are for rodents (e.g. mice (Mus musculus), leaf-eared mice (Phyllotis darwini) and bank voles (Clethrionomys glareolus)) probably because it is tractable to conduct experiments with appropriate breeding designs (Lacy & Lynch 1979;Bacigalupe et al 2004;Leamy et al 2005;Nespolo et al 2005;Sadowska et al 2005). Besides data for rodents, the heritability of basal metabolic rate (BMR) has been estimated for zebra finches (Taenopygia guttata; Rønning et al 2007), and the heritability of several measures of aerobic metabolism, including maximal metabolic rate (MMR), has been estimated for humans (Bouchard et al 1998;Perusse et al 2001).…”

Section: Introduction Energy Metabolism or Whatmentioning

confidence: 99%

Genetic variances and covariances of aerobic metabolic rates in laboratory mice

et al. 2009

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The genetic variances and covariances of traits must be known to predict how they may respond to selection and how covariances among them might affect their evolutionary trajectories. We used the animal model to estimate the genetic variances and covariances of basal metabolic rate (BMR) and maximal metabolic rate (MMR) in a genetically heterogeneous stock of laboratory mice. Narrow-sense heritability (h 2 ) was approximately 0.38 + 0.08 for body mass, 0.26 + 0.08 for whole-animal BMR, 0.24 + 0.07 for whole-animal MMR, 0.19 + 0.07 for mass-independent BMR, and 0.16 + 0.06 for mass-independent MMR. All h 2 estimates were significantly different from zero. The phenotypic correlation of whole animal BMR and MMR was 0.56 + 0.02, and the corresponding genetic correlation was 0.79 + 0.12. The phenotypic correlation of mass-independent BMR and MMR was 0.13 + 0.03, and the corresponding genetic correlation was 0.72 + 0.03. The genetic correlations of metabolic rates were significantly different from zero, but not significantly different from one. A key assumption of the aerobic capacity model for the evolution of endothermy is that BMR and MMR are linked. The estimated genetic correlation between BMR and MMR is consistent with that assumption, but the genetic correlation is not so high as to preclude independent evolution of BMR and MMR.

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“…Mice were lightly anesthetized with isofluorane then scanned, excluding the head, using PIXImus DEXA (Lunar Corporation, Madison, WI). Measurements and calculations were performed as previously described [52]. For analysis of DEXA data, males and females were pooled and put in two groups, either Ctgf Hi/+ or controls (including sibling controls of the genotypes Ctgf Lo/+;Cre- , Ctgf +/+; Cre + , or completely wild type).…”

Section: Methodsmentioning

confidence: 99%

A Mouse Strain Where Basal Connective Tissue Growth Factor Gene Expression Can Be Switched from Low to High

et al. 2010

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Connective tissue growth factor (CTGF) is a signaling molecule that primarily functions in extracellular matrix maintenance and repair. Increased Ctgf expression is associated with fibrosis in chronic organ injury. Studying the role of CTGF in fibrotic disease in vivo, however, has been hampered by perinatal lethality of the Ctgf null mice as well as the limited scope of previous mouse models of Ctgf overproduction. Here, we devised a new approach and engineered a single mutant mouse strain where the endogenous Ctgf-3′ untranslated region (3′UTR) was replaced with a cassette containing two 3′UTR sequences arranged in tandem. The modified Ctgf allele uses a 3′UTR from the mouse FBJ osteosarcoma oncogene (c-Fos) and produces an unstable mRNA, resulting in 60% of normal Ctgf expression (Lo allele). Upon Cre-expression, excision of the c-Fos-3′UTR creates a transcript utilizing the more stable bovine growth hormone (bGH) 3′UTR, resulting in increased Ctgf expression (Hi allele). Using the Ctgf Lo and Hi mutants, and crosses to a Ctgf knockout or Cre-expressing mice, we have generated a series of strains with a 30-fold range of Ctgf expression. Mice with the lowest Ctgf expression, 30% of normal, appear healthy, while a global nine-fold overexpression of Ctgf causes abnormalities, including developmental delay and craniofacial defects, and embryonic death at E10-12. Overexpression of Ctgf by tamoxifen-inducible Cre in the postnatal life, on the other hand, is compatible with life. The Ctgf Lo-Hi mutant mice should prove useful in further understanding the function of CTGF in fibrotic diseases. Additionally, this method can be used for the production of mouse lines with quantitative variations in other genes, particularly with genes that are broadly expressed, have distinct functions in different tissues, or where altered gene expression is not compatible with normal development.

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Genetic variance and covariance patterns for body weight and energy balance characters in an advanced intercross population of mice

Cited by 10 publications

References 26 publications

Quantitative trait mapping in Diversity Outbred mice identifies two genomic regions associated with heart size

Quantitative trait mapping in Diversity Outbred mice identifies two genomic regions associated with heart size

Genetic variances and covariances of aerobic metabolic rates in laboratory mice

A Mouse Strain Where Basal Connective Tissue Growth Factor Gene Expression Can Be Switched from Low to High

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