Genetic determinants of fibro-osseous lesions in aged inbred mice
| Autor: | Paul N. Schofield, Cheryl L. Ackert-Bicknell, Annerose Berndt, Kathleen A. Silva, Justin M M Cates, John P. Sundberg, Victoria E. Kennedy, Beth A. Sundberg |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Rodent Diseases Aging Candidate gene Pathology medicine.medical_specialty Clinical Biochemistry Mice Inbred Strains Single-nucleotide polymorphism Genome-wide association study Biology Article Pathology and Forensic Medicine Mice 03 medical and health sciences Sex Factors Inbred strain Bone Marrow Fibrosis medicine Animals Molecular Biology Chromosome medicine.disease Molecular biology 030104 developmental biology medicine.anatomical_structure Female Bone marrow Bone Diseases Genome-Wide Association Study |
| Zdroj: | Experimental and Molecular Pathology. 100:92-100 |
| ISSN: | 0014-4800 |
| DOI: | 10.1016/j.yexmp.2015.11.018 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect