Reference SummaryBerndt A, Exp Mol Pathol 2015 Nov 14;():

Title

Genetic Determinants of Fibro-osseous Lesions in Aged Inbred Mice.

Authors

Berndt A; Ackert-Bicknell C; Silva KA; Kennedy VE; Sundberg BA; Cates JM; Schofield PN; Sundberg JP

Journal

Exp Mol Pathol

Volume

Issue

Year

2015

Pages

Abstract

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.

Links

26589134 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
KK/HlJ Bone - Femur lesion - fibro-osseous Bone - Femur

observed

LP/J Bone - Femur lesion - fibro-osseous Bone - Femur

observed

KK/HlJ Bone - Skull lesion - fibro-osseous Bone - Skull

observed

129S1/SvImJ Bone lesion - fibro-osseous Bone

0 - 100

A/J Bone lesion - fibro-osseous Bone

0

BALB/cByJ Bone lesion - fibro-osseous Bone

0 - 13.33

BTBR T+ Itpr3tf/J Bone lesion - fibro-osseous Bone

0 - 33.33

BUB/BnJ Bone lesion - fibro-osseous Bone

0 - 50

C3H/HeJ Bone lesion - fibro-osseous Bone

0 - 7.69

C57BL/10J Bone lesion - fibro-osseous Bone

0 - 41.67

C57BL/6J Bone lesion - fibro-osseous Bone

0 - 13.33

C57BLKS/J Bone lesion - fibro-osseous Bone

0 - 8.33

C57BR/cdJ Bone lesion - fibro-osseous Bone

0 - 33.33

C57L/J Bone lesion - fibro-osseous Bone

0 - 6.67

CBA/J Bone lesion - fibro-osseous Bone

0 - 23.08

DBA/2J Bone lesion - fibro-osseous Bone

0 - 28.57

FVB/NJ Bone lesion - fibro-osseous Bone

0 - 37.5

KK/HlJ Bone lesion - fibro-osseous Bone

0 - 100

LP/J Bone lesion - fibro-osseous Bone

0 - 79.62

MRL/MpJ Bone lesion - fibro-osseous Bone

0 - 20

NOD.B10Sn-H2b/J Bone lesion - fibro-osseous Bone

0 - 12.5

NON/ShiLtJ Bone lesion - fibro-osseous Bone

0

NZO/HlLtJ Bone lesion - fibro-osseous Bone

0 - 33.33

NZW/LacJ Bone lesion - fibro-osseous Bone

0 - 100

P/J Bone lesion - fibro-osseous Bone

0 - 50

PL/J Bone lesion - fibro-osseous Bone

0

PWD/PhJ Bone lesion - fibro-osseous Bone

0

RIIIS/J Bone lesion - fibro-osseous Bone

0 - 28.57

SM/J Bone lesion - fibro-osseous Bone

0

SWR/J Bone lesion - fibro-osseous Bone

0 - 7.69

WSB/EiJ Bone lesion - fibro-osseous Bone

0 - 90.91