title: Bone loss in C57BL/6J-OlaHsd mice, a substrain of C57BL/6J carrying mutated alpha-synuclein and multimerin-1 genes.
abstract: The inbred mouse strain C57BL/6 is commonly used for the generation of transgenic mouse and is a well established strain in bone research. Different vendors supply different substrains of C57BL/6J as wild-type animals when genetic drift did not incur any noticeable phenotype. However, we sporadically observed drastic differences in the bone phenotype of "WT" C57BL/6J mice originating from different labs and speculated that these variations are attributable, at least in part, to the variation between C57BL/6J substrains, which is often overlooked. C57BL/6J-OlaHsd is a commonly used substrain that despite a well defined deletion in the alpha-synuclein (Snca) and multimerin-1 (Mmrn1) genes, was reported to display no obvious phenotype and is used as WT control. Here, we compared the bone phenotype of C57BL/6J-OlaHsd (6J-OLA) to C57BL/6J-RccHsd (6J-RCC) and to the original C57BL/6J (6J-JAX). Using μCT analysis, we found that 6J-OLA mice display a significantly lower trabecular bone mass compared to 6J-RCC and 6J-JAX. PCR analysis revealed that both the Snca and Mmrn1 genes are expressed in bone tissue of 6J-RCC animals but not of 6J-OLA mutants, suggesting either one or both genes play a role in bone metabolism. In vitro analysis demonstrated increase in osteoclasts number and decreased osteoblast mineralization in cells derived from 6J-OLA compared with 6J-RCC. Our data may shed light on unexplained differences in basal bone measurements between different research centers and reiterate the importance of specifying the exact substrain type. In addition, our findings describe the physiological role for Mmrn1 and/or Snca in bone remodeling.
authors.affiliation: Sackler Faculty of Medicine, Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Liron
authors.affiliation: Sackler Faculty of Medicine, Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Bitya
authors.initials: B
authors.lastname: Raphael
authors.affiliation: Sackler Faculty of Medicine, Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sahar
authors.initials: S
authors.lastname: Hiram-Bab
authors.affiliation: Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Itai A
authors.initials: IA
authors.lastname: Bab
authors.affiliation: Sackler Faculty of Medicine, Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yankel
authors.identifier: http://orcid.org/0000-0002-7494-0631
authors.initials: Y
authors.lastname: Gabet
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D015519:Bone Density; D016723:Bone Remodeling / Q000235:genetics*; D002113:Calcification, Physiologic; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010641:Phenotype; D055114:X-Ray Microtomography; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D015815:Cell Adhesion Molecules; C000594469:Mmrn1 protein, mouse; C497605:Snca protein, mouse; D051844:alpha-Synuclein
keywords: C57Bl/6J substrains; bone mass accrual; genetic drift; osteoporosis; peak bone mass