The mouse as a model for human biology: a resource guide for complex trait analysis

Peters, Luanne L.; Robledo, Raymond F.; Bult, Carol J.; Churchill, Gary A.; Paigen, Beverly; Svenson, Karen L.

doi:10.1038/nrg2025

Cited by 264 publications

(227 citation statements)

References 119 publications

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“…Mouse models have been critical for the identification of genes conferring risk for obesity (15,16) and cardiovascular disease (17). Thus, the mouse has become a key model for biomedical research (18). Of the currently available obese mouse models, the New Zealand Obese (NZO) mouse, a polygenic mutant on a New Zealand (NZ) background (19), is an excellent potential model for the study of obesity and whether obesity affects the size of upper airway structure.…”

mentioning

confidence: 99%

Altered Upper Airway and Soft Tissue Structures in the New Zealand Obese Mouse

Brennick¹,

Pack²,

Ko³

et al. 2009

Am J Respir Crit Care Med

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Rationale: The effect of obesity on upper airway soft tissue structure and size was examined in the New Zealand Obese (NZO) mouse and in a control lean mouse, the New Zealand White (NZW). Objectives: We hypothesized that the NZO mouse has increased volume of neck fat and upper airway soft tissues and decreased pharyngeal airway caliber. Methods: Pharyngeal airway size, volume of the upper airway soft tissue structures, and distribution of fat in the neck and body were measured using magnetic resonance imaging (MRI). Dynamic MRI was used to examine the differences in upper airway caliber between inspiration and expiration in NZO versus NZW mice. Measurements and Main Results:The data support the hypothesis that, in obese NZO versus lean NZW mice, airway caliber was significantly smaller (P , 0.03), with greater parapharyngeal fat pad volumes (P , 0.0001) and a greater volume of other upper airway soft tissue structures (tongue, P 5 0.003; lateral pharyngeal walls, P 5 0.01; soft palate, P 5 0.02). Dynamic MRI showed that the airway of the obese NZO mouse dilated during inspiration, whereas in the lean NZW mouse, the upper airway was reduced in size during inspiration. Conclusions: In addition to the increased volume of pharyngeal soft tissue structures, direct fat deposits within the tongue may contribute to airway compromise in obesity. Pharyngeal airway dilation during inspiration in NZO mice compared with narrowing in NZW mice suggests that airway compromise in obese mice may lead to muscle activation to defend upper airway patency during inspiration.

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mentioning

confidence: 99%

Altered Upper Airway and Soft Tissue Structures in the New Zealand Obese Mouse

Brennick¹,

Pack²,

Ko³

et al. 2009

Am J Respir Crit Care Med

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“…Dozens of inbred strains are available with sufficient genetic variability among them for linkage mapping and association studies (Paigen 2003a,b;Peters et al 2007). A variety of molecular genetic tools are available for the mouse, making it possible to identify and functionally characterize candidate genes for some traits.…”

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confidence: 99%

Nucleotide Variation in Wild and Inbred Mice

2007

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The house mouse is a well-established model organism, particularly for studying the genetics of complex traits. However, most studies of mice use classical inbred strains, whose genomes derive from multiple species. Relatively little is known about the distribution of genetic variation among these species or how variation among strains relates to variation in the wild. We sequenced intronic regions of five X-linked loci in large samples of wild Mus domesticus and M. musculus, and we found low levels of nucleotide diversity in both species. We compared these data to published data from short portions of six X-linked and 18 autosomal loci in wild mice. We estimate that M. domesticus and M. musculus diverged ,500,000 years ago. Consistent with this recent divergence, some gene genealogies were reciprocally monophyletic between these species, while others were paraphyletic or polyphyletic. In general, the X chromosome was more differentiated than the autosomes. We resequenced classical inbred strains for all 29 loci and found that inbred strains contain only a small amount of the genetic variation seen in wild mice. Notably, the X chromosome contains proportionately less variation among inbred strains than do the autosomes. Moreover, variation among inbred strains derives from differences between species as well as from differences within species, and these proportions differ in different genomic regions. Wild mice thus provide a reservoir of additional genetic variation that may be useful for mapping studies. Together these results suggest that wild mice will be a valuable complement to laboratory strains for studying the genetics of complex traits.

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“…Each RI population is a series of strains of mice descended from two or more progenitor strains but which has been bred to homozygousity. 23 Thus, unlike an F2 mouse, wherein each one is a genetic one in a million, the combination of alleles found in any one RI mouse is mirrored by all other RI mice of that same strain.…”

Section: Types Of Genetic Studies Conductedmentioning

confidence: 99%

“…[26][27][28][29] Additional study designs have been used to better define the genetic etiology of bone strength, including the use of congenic and consomic genetic reference populations. 23 A consomic, which is sometimes referred to as chromosome substitution, is a strain wherein all of the alleles for an entire chromosome from one inbred strain of mice or rats have been moved onto an otherwise pure background of a second strain. Similarly, a congenic is a strain with part of a chromosome moved from one genetic background to another.…”

Section: Types Of Genetic Studies Conductedmentioning

confidence: 99%

“…Covering the possible bioinformatics approaches that could be applied is beyond the scope of this review. The reviews by Peters et al 23 and DiPetrillo et al 40 provide details of these methods. Many of these techniques were originally developed for use with mouse QTL and could just as easily be applied to the QTL described in Table 1.…”

Section: Phenotypes Of Bone Strengthmentioning

confidence: 99%

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Genetic regulation of bone strength: a review of animal model studies

Adams¹,

Ackert‐Bicknell²

2015

BoneKEy Reports

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Population-and family-based studies have established that fragility fracture risk is heritable; yet, the genome-wide association studies published to date have only accounted for a small fraction of the known variation for fracture risk of either the femur or the lumbar spine. Much work has been carried out using animal models toward finding genetic loci that are associated with bone strength. Studies using animal models overcome some of the issues associated with using patient data, but caution is needed when interpreting the results. In this review, we examine the types of tests that have been used for forward genetics mapping in animal models to identify loci and/or genes that regulate bone strength and discuss the limitations of these test methods. In addition, we present a summary of the quantitative trait loci that have been mapped for bone strength in mice, rats and chickens. The majority of these loci co-map with loci for bone size and/or geometry and thus likely dictate strength via modulating bone size. Differences in bone matrix composition have been demonstrated when comparing inbred strains of mice, and these matrix differences may be associated with differences in bone strength. However, additional work is needed to identify loci that act on bone strength at the materials level.

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The mouse as a model for human biology: a resource guide for complex trait analysis

Cited by 264 publications

References 119 publications

Altered Upper Airway and Soft Tissue Structures in the New Zealand Obese Mouse

Altered Upper Airway and Soft Tissue Structures in the New Zealand Obese Mouse

Nucleotide Variation in Wild and Inbred Mice

Genetic regulation of bone strength: a review of animal model studies

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