Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes

Bone Research
Delphine B MaurelL F Bonewald

Abstract

Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology, function and disease. While numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts, few target osteocytes specifically, particularly mature osteocytes. Our goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a Bac construct containing the 5' and 3' regions of the Sost gene (Sost ERT2 Cre). Four founder lines were crossed with the Ai9 Cre reporter mice. One founder line showed high and specific activity in mature osteocytes. Bones and organs were imaged and fluorescent signal quantitated. While no activity was observed in 2 day old pups, by 2 months of age some osteocytes were positive as osteocyte Cre activity became spontaneous or 'leaky' with age. The percentage of positive osteocytes increased following tamoxifen injection, especially in males, with 43% to 95% positive cells compared to 19% to 32% in females. No signal was observed in any bone surface cell, bone marrow, nor in muscle with or without tamoxifen injection. No spontaneous signal was observed in any other organ. However, with tamox...Continue Reading

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Citations

Oct 5, 2019·Journal of Bone and Mineral Metabolism·Mitsutaka YakabeSumito Ogawa
Feb 11, 2020·Annual Review of Physiology·Alexander G Robling, Lynda F Bonewald
Jan 10, 2021·Current Osteoporosis Reports·Xuehua LiJinhu Xiong
Jun 4, 2020·Cell Reports·Julia A WagnerTodd A Fehniger
Jul 20, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Greig CouasnayFlorent Elefteriou
Aug 3, 2021·Physiological Reviews·Jesus Delgado-Calle, Teresita Bellido

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Datasets Mentioned

BETA
GSE119761

Methods Mentioned

BETA
transgenic
confocal microscopy
x-ray
RNAseq
RNA-Seq
PCR
targeted mutation
genotyping
fluorescence imaging

Software Mentioned

AnalySIS
Protein ANalysis THrough Evolutionary Relationships ( PANTHER )
ADI
NanoDrop
FastQC
featureCounts
STAR RNA - seq aligner
MultiQC
LAS
PowerLab

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