Inducible Cre transgenic mouse strain for skeletal muscle-specific gene targeting

McCarthy, John J.; Srikuea, Ratchakrit; Kirby, Tyler J.; Peterson, Charlotte A.; Esser, Karyn A.

doi:10.1186/2044-5040-2-8

Cited by 158 publications

(190 citation statements)

References 29 publications

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“…Moreover, in osteoblasts, maturation-dependent CRE drivers [54–59] will allow us to identify the stage at which osteoblasts are most sensitive to signals of muscle origin. The same is true of myoblast CRE drivers [60–66]. Several of these now allow induction of CRE activity, so that animal age as well as developmental stage of the target cells can be experimentally controlled [59, 61, 65, 66].…”

Section: Directions For Future Researchmentioning

confidence: 99%

“…The same is true of myoblast CRE drivers [60–66]. Several of these now allow induction of CRE activity, so that animal age as well as developmental stage of the target cells can be experimentally controlled [59, 61, 65, 66]. Together, these genetic tools will allow investigators to map both genes and their tissues to unravel the mechanisms by which bone and muscle communicate.…”

Section: Directions For Future Researchmentioning

confidence: 99%

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Bone and Muscle Pleiotropy: The Genetics of Associated Traits

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2014

Clinic Rev Bone Miner Metab

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Bone and muscle mass are highly correlated. In part, this is a consequence of both tissues sharing common genetic determinants. In addition, both tissues are responsive to their mechanical environments. New genetic tools in mice will allow genes of interest to be inactivated in experimentally defined contexts, thus allowing investigators to distinguish direct effects on each tissue from physiological responses to a primary phenotype in the other.

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Section: Directions For Future Researchmentioning

confidence: 99%

Section: Directions For Future Researchmentioning

confidence: 99%

Bone and Muscle Pleiotropy: The Genetics of Associated Traits

Blank

2014

Clinic Rev Bone Miner Metab

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“…Ideally, mouse models displaying skeletal muscle specific EPO-R knockout or over expression would be an important tool to assess the direct importance and role of EPO and EPO-R in skeletal muscle. The use of a Cre/loxP system to specifically knockout a target of interest in mouse skeletal muscle in vivo has been developed (McCarthy et al, 2012). This inducible model is able to overcome limitations of traditional gene targeting strategies and can down regulate the target of interest in a temporal and tissue-specific manner in the adult animal following tamoxifen administration.…”

Section: Effects Of Epo In Skeletal Musclementioning

confidence: 99%

The role and regulation of erythropoietin (EPO) and its receptor in skeletal muscle: how much do we really know?

Lamon¹,

Russell²

2013

Front. Physiol.

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Erythropoietin (EPO) primarily activates erythroid cell proliferation and growth and is active in several types of non-hematopoietic cells via its interaction with the EPO-receptor (EPO-R). This review focuses on the role of EPO in skeletal muscle. The EPO-R is expressed in skeletal muscle cells and EPO may promote myoblast differentiation and survival via the activation of the same signaling cascades as in hematopoietic cells, such as STAT5, MAPK and Akt. Inconsistent results exist with respect to the detection of the EPO-R mRNA and protein in muscle cells, tissue and across species and the use of non-specific EPO-R antibodies contributes to this problem. Additionally, the inability to reproducibly detect an activation of the known EPO-induced signaling pathways in skeletal muscle questions the functionality of the EPO-R in muscle in vivo. These equivocal findings make it difficult to distinguish between a direct effect of EPO on skeletal muscle, via the activation of its receptor, and an indirect effect resulting from a better oxygen supply to the muscle. Consequently, the precise role of EPO in skeletal muscle and its regulatory mechanism/s remain to be elucidated. Further studies are required to comprehensively establish the importance of EPO and its function in skeletal muscle health.

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“…Of note, the amount of pericyte ablation in Tg:NG2 cre/+ ::R26R iDTR mice was higher than predicted by lacZ reporter gene expression, and, in addition, it differed in adult and pup experiments. The non-linear relationship between X-gal staining intensity and the level of recombination has been previously documented in different muscle areas, and attributed to differences in activity of the ROSA26 promoter or to the stability of β-gal protein across different muscle areas (McCarthy et al, 2012). Minor iDTR expression at the cell surface may be sufficient to confer sensitivity to DT, whereas minute amounts of β-gal diluted into the cytosol may not be detectable microscopically.…”

Section: Post-natal Ablation Of Muscle Pericytesmentioning

confidence: 99%

Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence

et al. 2015

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The satellite cells, which serve as adult muscle stem cells, are both located beneath myofiber basement membranes and closely associated with capillary endothelial cells. We observed that 90% of capillaries were associated with pericytes in adult mouse and human muscle. During post-natal growth, newly formed vessels with their neuroglial 2 proteoglycan (NG2)-positive pericytes became progressively associated with the post-natal muscle stem cells, as myofibers increased in size and satellite cells entered into quiescence. In vitro, human muscle-derived pericytes promoted myogenic cell differentiation through insulin-like growth factor 1 (IGF1) and myogenic cell quiescence through angiopoietin 1 (ANGPT1). Diphtheria toxin-induced ablation of muscle pericytes in growing mice led both to myofiber hypotrophy and to impaired establishment of stem cells quiescence. Similar effects were observed following conditional in vivo deletion of pericyte Igf1 and Angpt1 genes, respectively. Our data therefore demonstrate that, by promoting post-natal myogenesis and stem cell quiescence, pericytes play a key role in the microvascular niche of satellite cells.

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Inducible Cre transgenic mouse strain for skeletal muscle-specific gene targeting

Cited by 158 publications

References 29 publications

Bone and Muscle Pleiotropy: The Genetics of Associated Traits

Bone and Muscle Pleiotropy: The Genetics of Associated Traits

The role and regulation of erythropoietin (EPO) and its receptor in skeletal muscle: how much do we really know?

Pericytes in the myovascular niche promote post-natal myofiber growth and satellite cell quiescence

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