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Characterization of bone morphology in CCN5/WISP5 knockout mice
Jie Jiang1, Gexin Zhao2,3, Karen M Lyons4,5
1Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA.
Abstract:
CCN5/WISP2 is part of the CCN family of matricellular proteins, but is distinct in that it lacks the C-terminal (CT) domain. Although CCN5 has been shown to impact cell proliferation and differentiation in vitro, its role in vivo is unclear. We therefore generated mice using ES cells developed by the Knockout Mouse Project (KOMP) in which exons 2-5, which encode the all of the conserved protein coding regions, are replaced by a lacZ cassette. Ccn5 LacZ/LacZ mice were viable and apparently normal. Based on previous studies showing that CCN5 impacts osteoblast proliferation and differentiation, we performed an analysis of adult bone phenotype. LacZ expression was examined in adult bone, and was found to be strong within the periosteum, but not in trabecular bone or bone marrow. Micro-CT analysis revealed no apparent changes in bone mineral density (BMD) or bone tissue volume (BV/TV) in Ccn5 LacZ/LacZ mice. These studies indicate that CCN5 is not required for normal bone formation, but they do not rule out a role in mechanotransduction or repair processes. The availability of Ccn5 LacZ mice enables studies of CCN5 expression and function in multiple tissues.
Insights
CCN5 (Cell-Cell Nucleus 5) protein is not essential for normal bone formation in mice. Studies using Ccn5 knockout mice show no changes in bone density, but suggest potential roles in other processes.
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- CCN5/WISP2 is a matricellular protein lacking a C-terminal domain.
- Previous in vitro studies suggest CCN5 influences cell proliferation and differentiation.
- The in vivo function of CCN5 remains largely uncharacterized.
Purpose of the Study:
- To investigate the in vivo role of CCN5 in adult bone homeostasis.
- To characterize the phenotype of Ccn5 knockout mice.
Main Methods:
- Generated Ccn5 knockout mice (Ccn5 LacZ/LacZ) using KOMP ES cells.
- Analyzed lacZ expression in adult bone tissues.
- Performed Micro-CT analysis to assess bone mineral density (BMD) and bone tissue volume (BV/TV).
Main Results:
- Ccn5 LacZ/LacZ mice were viable and phenotypically normal.
- LacZ expression was detected in the periosteum but not in trabecular bone or bone marrow.
- No significant alterations in BMD or BV/TV were observed in knockout mice.
Conclusions:
- CCN5 is not required for normal adult bone formation.
- These findings do not exclude a role for CCN5 in bone mechanotransduction or repair.
- Ccn5 knockout mice provide a valuable tool for studying CCN5 function in various tissues.
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