High-efficiency somatic mutagenesis in smooth muscle cells and cardiac myocytes in SM22?-Cre transgenic mice

Lepore, John J.; Cheng, Lan; Lü, Min; Mericko, Patricia; Morrisey, Edward E.; Parmacek, Michael S.

doi:10.1002/gene.20112

Cited by 101 publications

(138 citation statements)

References 15 publications

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“…On Western blot analysis of GR protein from hearts of control and Sm-22 Creϩ GR loxP/loxP mouse pairs, we found that, if anything, heart GR was slightly increased and certainly not decreased in Sm-22 Creϩ GR loxP/loxP mice ( Figure 4B), suggesting that there was no significant GR deletion from cardiac myocytes in our KO mice. Consistent with this and previous studies, 15,16 we found no differences in heart rate between the two groups either before or after DEX administration ( Figure 5). Our data suggest a critical role of VSM GR on the acute hypertensive response to GC.…”

Section: No Apparent Role For Vsm Gr In Basal Bp Regulationsupporting

confidence: 93%

“…BP measured at 14 d showed that Sm-22 Creϩ GR loxP/loxP mice maintained a MAP of 121.0 Ϯ 5.3 mmHg and controls maintained a MAP of 119.2 Ϯ 3.1 mmHg (P ϭ 0.36), suggesting that Sm-22 Creϩ GR loxP/loxP mice likely attain the same rise in BP observed in the controls with continued DEX therapy. Previous studies that have used Sm-22 Cre in the generation of transgenic mice have suggested that Sm-22 Cre is expressed at high levels in murine cardiac muscle 15 ; however, in the Sm-22 Cre model we used, only minimal cardiac expression was observed. 13 To determine whether GC effects on cardiac muscle could underlie the BP phenotype we observed in our model, we assessed GR staining in the cardiac muscle of Sm-22 Creϩ GR loxP/loxP and control mice and found no significant difference between Creϩ and CreϪ littermates ( Figure 4A).…”

Section: No Apparent Role For Vsm Gr In Basal Bp Regulationmentioning

confidence: 84%

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A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

Goodwin¹,

Zhang²,

Geller³

2008

Journal of the American Society of Nephrology

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Although glucocorticoid (GC)-induced hypertension has commonly been attributed to promiscuous activation of the mineralocorticoid receptor by cortisol, thereby promoting excess reabsorption of sodium and water, numerous lines of evidence indicate that this is not the only or perhaps even the primary mechanism. GC induce a number of effects on vascular smooth muscle (VSM) in vitro that may be pertinent to hypertension, but their contribution in vivo is unknown. To address this question, a mouse model with a tissue-specific knockout (KO) of the GC receptor in the VSM was created and characterized. Similar to control mice, KO mice exhibited normal baseline BP and, interestingly, showed normal circadian variation in BP. When dexamethasone was administered, however, the acute hypertensive response was markedly attenuated in KO mice, and there was a trend toward a decreased chronic hypertensive response. These data suggest that the GC receptor in VSM plays a critical role in the acute hypertensive response to GC in vivo.

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Section: No Apparent Role For Vsm Gr In Basal Bp Regulationsupporting

confidence: 93%

Section: No Apparent Role For Vsm Gr In Basal Bp Regulationmentioning

confidence: 84%

A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

Goodwin¹,

Zhang²,

Geller³

2008

Journal of the American Society of Nephrology

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“…This report shows for the first time that the cytoskeletal protein transgelin [65] exists in longterm stimulated skeletal muscles. Transgelin, also referred to as SM22a [66], has been localized to vascular smooth muscle cells throughout the arterial and venous system. It has been described in visceral smooth muscle cells in various organs and the heart, but as being absent from mature skeletal muscle [66].…”

Section: Discussionmentioning

confidence: 99%

“…Transgelin, also referred to as SM22a [66], has been localized to vascular smooth muscle cells throughout the arterial and venous system. It has been described in visceral smooth muscle cells in various organs and the heart, but as being absent from mature skeletal muscle [66]. The electrostimulation-dependent induction revealed by DIGE analysis suggests transgelin as another excellent biomarker of fast-to-slow fibre transition.…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of chronic low‐frequency stimulated fast muscle

et al. 2007

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Skeletal muscle fibre transitions occur in many biological processes, in response to alterations in neuromuscular activity, in muscular disorders, during age-induced muscle wasting and in myogenesis. It was therefore of interest to perform a comprehensive proteomic profiling of muscle transformation. Chronic low-frequency stimulation of the rabbit tibialis anterior muscle represents an established model system for studying the response of fast fibres to enhanced neuromuscular activity under conditions of maximum activation. We have conducted a DIGE analysis of unstimulated control specimens versus 14-and 60-day conditioned muscles. A differential expression pattern was observed for 41 protein species with 29 increased and 12 decreased muscle proteins. Identified classes of proteins that are changed during the fast-to-slow transition process belong to the contractile machinery, ion homeostasis, excitation-contraction coupling, capillarization, metabolism and stress response. Results from immunoblotting agreed with the conversion of the metabolic, regulatory and contractile molecular apparatus to support muscle fibres with slower twitch characteristics. Besides confirming established muscle elements as reliable transition markers, this proteomics-based study has established the actin-binding protein cofilin-2 and the endothelial marker transgelin as novel biomarkers for evaluating muscle transformation.

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“…This phenotypic variation in 2 different promoters likely relates to the activation time and the strength of each promoter. Indeed, SM22α-Cre is activated earlier at E9.5 16,27 than Myh11-Cre at E13.5. 28 SM22α (Tagln) is expressed higher than Myh11 in jejunal and colon SMCs.…”

Section: Serum Response Factor Knockout Phenotypementioning

confidence: 95%

Multi-phenotypic Role of Serum Response Factor in the Gastrointestinal System

2016

J Neurogastroenterol Motil

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Serum response factor (SRF) is a master transcription factor of the actin cytoskeleton that binds to highly conserved CArG boxes located within the majority of smooth muscle cell (SMC)-restricted promoters/enhancers. Although most studies of SRF focus on skeletal muscle, cardiac muscle, and vascular SMCs, SRF research has recently expanded into the gastrointestinal (GI) system. Genome scale analyses of GI SMC transcriptome and CArG boxes (CArGome) have identified new SRF target genes. In addition to circular and longitudinal smooth muscle layers, SRF is also expressed in GI mucosa and cancers. In the GI tract, SRF is the central regulator of genes involved in apoptosis, dedifferentiation, proliferation, and migration of cells. Since SRF is the cell phenotypic modulator, it may play an essential role in the development of myopathy, hypertrophy, ulcers, gastric and colon cancers within the GI tract. Given the multifunctional role displayed by SRF in the digestive system, SRF has received more attention emerging as a potential therapeutic target. This review summarizes the findings in SRF research pertaining to the GI tract and provides valuable insight into future directions.

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High-efficiency somatic mutagenesis in smooth muscle cells and cardiac myocytes in SM22?-Cre transgenic mice

Cited by 101 publications

References 15 publications

A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension

Proteomic profiling of chronic low‐frequency stimulated fast muscle

Multi-phenotypic Role of Serum Response Factor in the Gastrointestinal System

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