Schlafen2 mutation in mice causes an osteopetrotic phenotype due to a decrease in the number of osteoclast progenitors

Scientific Reports
Ibrahim OmarNoam Levaot

Abstract

Osteoclasts are the bone resorbing cells that derive from myeloid progenitor cells. Although there have been recent advancements in the ability to identify osteoclast progenitors, very little is known about the molecular mechanisms governing their homeostasis. Here, by analyzing the normalized phylogenetic profiles of the Schlafen (Slfn) gene family, we found that it co-evolved with osteoclast-related genes. Following these findings, we used a Slfn2 loss-of-function mutant mouse, elektra, to study the direct role of Slfn2 in osteoclast development and function. Slfn2eka/eka mice exhibited a profound increase in their cancellous bone mass and a significant reduction in osteoclast numbers. In addition, monocyte cultures from the bone marrow of Slfn2eka/eka mice showed a reduction in osteoclast number and total resorption area. Finally, we show that the bone marrow of Slfn2eka/eka mice have significantly less CD11b-Ly6Chi osteoclast precursors. Overall, our data suggest that Slfn2 is required for normal osteoclast differentiation and that loss of its function in mice results in an osteopetrotic phenotype.

References

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Citations

Feb 19, 2021·Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft·Michael J F Blumer
May 1, 2021·NAR Genomics and Bioinformatics·Tomer TsabanYuval Tabach

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Methods Mentioned

BETA
phylogenetic profiling
phylogenetic profiles
phylogenetic profile
flow cytometry

Software Mentioned

GeneAnaltyics
gplots
R
SPIN
Gene Analytics
CellSens
ImageJ

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