Phenotypic Characterization of the KK/HlJ Inbred Mouse Strain

Berndt, Annerose; Sundberg, Beth A.; Silva, Kathleen A.; Kennedy, Victoria E.; Richardson, M; Li, Qiaoli; Bronson, Roderick T.; Uitto, Jouni; Sundberg, John P.

doi:10.1177/0300985813501335

Cited by 17 publications

(16 citation statements)

References 32 publications

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“…KK mice are a polygenic obese mouse model for diabetes mellitus type 2 due to their inherited glucose intolerance and insulin resistance. They develop DMT2 in response to high fat diet and usually during aging (Ikeda, 1994;Herberg and Coleman, 1977;Berndt et al, 2014). Similarly, NZO develop an early onset DMT2 due to obesity and are used as model for peripheral neuropathy and treatment of diabetic neuropathic pain (Zhang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Thirty Mouse Strain Survey of Voluntary Physical Activity and Energy Expenditure: Influence of Strain, Sex and Day–Night Variation

et al. 2020

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We measured indirect calorimetry and activity parameters, VO 2 and VCO 2 to extract respiratory exchange ratio (RER) and energy expenditure in both sexes of 30 inbred mouse strains of 6 genetic families at 9-13 weeks during one photophase and the subsequent scotophase. We observed a continuous distribution of all traits. While males had higher body weights than females, we observed no sex difference for food and water intake. All strains drank and fed more during the night even if they displayed no day-night difference in activity traits. Several strains showed absent or weak daynight variation in one or more activity traits and these included FVB and 129X1, males of 129S1, SWR, NZW, and SM, and females of SJL. In general females showed higher rearing and ambulatory activity with 6 and 9 strains, respectively, showing a sex difference. Fine motor movements, like grooming, showed less sex differences. RER underlied a strong day-night difference and no sex effect. Only FVB females and males of the RIIIS and SM strain had no day-night variation. Energy expenditure underlies a large day-night variation which was absent in SWR and in FVB females and RIIIS males. In general, female bodies had a tendency to higher energy expenditure values, which became a significant difference in C3H, MAMy, SM, DBA1, and BUB. Our data illustrate the diversity of these traits in male and female inbred mice and provide a resource in the selection of strains for future studies.

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Section: Discussionmentioning

confidence: 99%

Thirty Mouse Strain Survey of Voluntary Physical Activity and Energy Expenditure: Influence of Strain, Sex and Day–Night Variation

et al. 2020

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“…The most severely affected inbred strain in the study reported here (i.e., KK/HlJ) also develops systemic ectopic mineralization suggestive of a pseudoxanthoma elasticum-like (PXE-like) disease (Berndt et al, 2013; Berndt et al, 2014; Li et al, 2012). Fibro-osseous lesions suggest abnormalities in bone formation, which could be another aspect of the PXE-like disease.…”

Section: Discussionmentioning

confidence: 68%

Genetic determinants of fibro-osseous lesions in aged inbred mice

Berndt

Ackert‐Bicknell

Silva

et al. 2016

Experimental and Molecular Pathology

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Fibro-osseous lesions in mice are progressive aging changes in which the bone marrow is replaced to various degrees by fibrovascular stroma and bony trabeculae in a wide variety of bones. The frequency and severity varied greatly among 28 different inbred mouse stains, predominantly affecting females, ranging from 0% for 10 strains to 100% for KK/HlJ and NZW/LacJ female mice. Few lesions were observed in male mice and for 23 of the strains, no lesions were observed in males for any of the cohorts. There were no significant correlations between strain-specific severities of fibro-osseous lesions and ovarian (r=0.11; P=0.57) or endometrial (r=0.03; P=0.89) cyst formation frequency or abnormalities in parathyroid glands. Frequency of fibro-osseous lesions was most strongly associated (P < 10−6) with genome variations on chromosome (Chr) 8 at 90.6 and 90.8 Mb (rs33108071, rs33500669; P = 5.0 · 10−10, 1.3 · 10−6), Chr 15 at 23.6 and 23.8 Mb (rs32087871, rs45770368; P = 7.3 · 10−7, 2.7 · 10−6), and Chr 19 at 33.2, 33.4, and 33.6 Mb (rs311004232, rs30524929, rs30448815; P=2.8 · 10−6, 2.8 · 10−6, 2.8 · 10−6) in genome-wide association studies (GWAS). The relatively large number of candidate genes identified in the GWAS analyses suggests that this may be an extremely complex polygenic disease. These results indicate that fibro-osseous lesions are surprisingly common in many inbred strains of laboratory mice as they age. While this presents little problem in most studies that utilize young animals, it may complicate aging studies, particularly those focused on bone.

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“…When mice that model ectopic mineralization are placed on diets with increased phosphate and reduced magnesium (‘acceleration diet’), the speed of development and the distribution of lesions are changed ( Li et al, 2014 ). For example, epicardial mineralization and fibrosis are commonly observed in old KK/HlJ mice on standard mouse diets ( Berndt et al, 2014 ) but, when the mice are placed on the ‘acceleration diet’, mineralization and fibrosis becomes multifocal, involving the entire myocardium and infrequently the epicardium alone (Quiaoli Li, Jouni Uitto and J.P.S., unpublished data).…”

Section: Impact Of Dietmentioning

confidence: 99%

Show and tell: disclosure and data sharing in experimental pathology

Schofield

Ward

Sundberg

2016

Disease Models &Amp; Mechanisms

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Reproducibility of data from experimental investigations using animal models is increasingly under scrutiny because of the potentially negative impact of poor reproducibility on the translation of basic research. Histopathology is a key tool in biomedical research, in particular for the phenotyping of animal models to provide insights into the pathobiology of diseases. Failure to disclose and share crucial histopathological experimental details compromises the validity of the review process and reliability of the conclusions. We discuss factors that affect the interpretation and validation of histopathology data in publications and the importance of making these data accessible to promote replicability in research.

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Phenotypic Characterization of the KK/HlJ Inbred Mouse Strain

Cited by 17 publications

References 32 publications

Thirty Mouse Strain Survey of Voluntary Physical Activity and Energy Expenditure: Influence of Strain, Sex and Day–Night Variation

Thirty Mouse Strain Survey of Voluntary Physical Activity and Energy Expenditure: Influence of Strain, Sex and Day–Night Variation

Genetic determinants of fibro-osseous lesions in aged inbred mice

Show and tell: disclosure and data sharing in experimental pathology

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