The 2.3 kb smooth muscle myosin heavy chain promoter directs gene expression into the vascular system of transgenic mice and rabbits,

Franz, Wolfgang M.; Mueller, Oliver J; Fleischmann, Michaela; Babij, Philip; Frey, Norbert; Müeller, Matthias; Besenfelder, U.; Moorman, Antoon F.M.; Brem, Gottfried; Katus, Hugo A.

doi:10.1016/s0008-6363(99)00173-x

Cited by 13 publications

(5 citation statements)

References 30 publications

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“…Smooth muscle ␣-actin is highly expressed in adult vascular smooth muscle but has recently been shown to be expressed at significantly lower levels in adult visceral muscle (45). Smooth muscle myosin heavy chain is widely expressed in smooth muscle tissues (41); however, a 2.3-kb fragment of the promoter region drives expression of a transgene predominantly in vascular tissue (25). Although the immunostaining data are suggestive, it is not known whether the poly-Tmod antibody recognizes all 40-kDa Tmod isoforms with equal affinity.…”

Section: Discussionmentioning

confidence: 99%

Leiomodin and tropomodulin in smooth muscle

Conley

2001

American Journal of Physiology-Cell Physiology

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Evidence is accumulating to suggest that actin filament remodeling is critical for smooth muscle contraction, which implicates actin filament ends as important sites for regulation of contraction. Tropomodulin (Tmod) and smooth muscle leiomodin (SM-Lmod) have been found in many tissues containing smooth muscle by protein immunoblot and immunofluorescence microscopy. Both proteins cofractionate with tropomyosin in the Triton-insoluble cytoskeleton of rabbit stomach smooth muscle and are solubilized by high salt. SM-Lmod binds muscle tropomyosin, a biochemical activity characteristic of Tmod proteins. SM-Lmod staining is present along the length of actin filaments in rat intestinal smooth muscle, while Tmod stains in a punctate pattern distinct from that of actin filaments or the dense body marker alpha-actinin. After smooth muscle is hypercontracted by treatment with 10 mM Ca(2+), both SM-Lmod and Tmod are found near alpha-actinin at the periphery of actin-rich contraction bands. These data suggest that SM-Lmod is a novel component of the smooth muscle actin cytoskeleton and, furthermore, that the pointed ends of actin filaments in smooth muscle may be capped by Tmod in localized clusters.

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Section: Discussionmentioning

confidence: 99%

Leiomodin and tropomodulin in smooth muscle

Conley

2001

American Journal of Physiology-Cell Physiology

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“…[7][8][9][10][11][12][13][14] However, each of these promoters mediates a distinct pattern of transgene expression. For example a 2.4-kb fragment of the rabbit telokin promoter directs high levels of transgene expression in smooth muscles of the gut, airways, and reproductive and urinary tracts and low levels of expression in vascular smooth muscle.…”

mentioning

confidence: 99%

“…8 In contrast, truncated myosin gene fragments direct different patterns of transgene expression depending on the precise deletions made. 9,12 The pattern of expression of these transgenes in various smooth muscle tissues suggests that distinct regulatory elements or modules, as well as distinct transcription factors, are required for the expression of a single gene in different smooth muscle tissues. This is further supported by results obtained from analysis of the SM22␣ promoter in transgenic mice.…”

mentioning

confidence: 99%

Cell-Specific Regulatory Modules Control Expression of Genes in Vascular and Visceral Smooth Muscle Tissues

Hoggatt

Simon

Herring

2002

Circulation Research

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Abstract-A novel approach with chimeric SM22␣/telokin promoters was used to identify gene regulatory modules that are required for regulating the expression of genes in distinct smooth muscle tissues. Conventional deletion or mutation analysis of promoters does not readily distinguish regulatory elements that are required for basal gene expression from those required for expression in specific smooth muscle tissues. In the present study, the mouse telokin gene was isolated, and a 370-bp (Ϫ190 to 180) minimal promoter was identified that directs visceral smooth muscle-specific expression in vivo in transgenic mice. The visceral smooth muscle-specific expression of the telokin promoter transgene is in marked contrast to the reported arterial smooth muscle-specific expression of a 536-bp minimal SM22␣ (Ϫ475 to 61) promoter transgene. To begin to identify regulatory elements that are responsible for the distinct tissue-specific expression of these promoters, a chimeric promoter in which a 172-bp SM22␣ gene fragment (Ϫ288 to Ϫ116) was fused to the minimal telokin promoter was generated and characterized. The Ϫ288 to Ϫ116 SM22␣ gene fragment significantly increased telokin promoter activity in vascular smooth muscle cells in vitro and in vivo. Conversely, a fragment of the telokin promoter (Ϫ94 to Ϫ49) increased the activity of the SM22␣ promoter in visceral smooth muscle cells of the bladder. Together, these data demonstrate that both vascular-and visceral smooth muscle-specific regulatory modules direct gene expression in subsets of smooth muscle tissues. Key Words: SM22␣ Ⅲ telokin Ⅲ gene regulation S mooth muscle cells arise from diverse populations of precursor cells during embryonic development, and the mechanisms that specify the smooth muscle cell phenotype in each of these populations of cells are largely unknown. All differentiated smooth muscle is characterized by the presence of unique isoforms of contractile proteins (such as smooth muscle ␣-and ␥-actin, myosin heavy chain, caldesmon, SM22␣, telokin, and calponin) that are not expressed in other tissue types. Analysis of the spatial and temporal pattern of expression of several smooth muscle proteins has revealed distinct patterns of expression of these proteins in different smooth muscle tissues during development. [1][2][3][4][5][6] This suggests that it is likely that distinct and overlapping mechanisms control the expression of genes in different smooth muscle tissues. The heterogeneity of regulatory mechanisms likely reflects the diverse embryological origins of smooth muscle cells in these different tissues.The cis-acting regulatory elements of the SM22␣, telokin, smooth muscle myosin heavy chain, smooth muscle ␣-and ␥-actin, and desmin genes have been shown to direct reporter gene expression to smooth muscle tissues in transgenic mice. [7][8][9][10][11][12][13][14] However, each of these promoters mediates a distinct pattern of transgene expression. For example a 2.4-kb fragment of the rabbit telokin promoter directs high levels of transgene express...

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“…The human PDGF b-chain promoter used in Line #5 was shown to drive reporter gene expression in the brain, overlapping with antibody expression studies in the non-human primate brain (Sasahara et al 1991), whereas the human GFAP promoter in Line #16 was shown to direct reporter lacZ expression to astrocytes in transgenic mice and in cultured human cells (Brenner et al 1994). Line#20 (SMHC-CreERT2) contains the rabbit SMHC promoter shown to direct luciferase expression specifically in vascular smooth muscle cells of large arteries including coronary arteries in transgenic mice and rabbits (Franz et al 1999). Given these data, these promoters are highly likely to have a similar cell-specific activity in transgenic rats.…”

Section: Discussionmentioning

confidence: 92%

“…Line#20 (SMHC-CreERT2) contains a 2.3-kb promoter of the rabbit smooth muscle myosin heavy chain (SMHC) gene. This promoter was shown to direct luciferase expression specifically in vascular smooth muscle cells of large arteries including coronary arteries in transgenic mice and rabbits (Franz et al 1999). This promoter is likely to have a similar cellspecific activity in transgenic rats.…”

Section: Lines Made Using Targatt Tmmentioning

confidence: 95%

Establishment of a Cre-rat resource for creating conditional and physiological relevant models of human diseases

2021

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The goal of this study is to establish a Cre/loxP rat resource for conditional and physiologically predictive rat models of human diseases. The laboratory rat (R. norvegicus) is a central experimental animal in several fields of biomedical research, such as cardiovascular diseases, aging, infectious diseases, autoimmunity, cancer models, transplantation biology, inflammation, cancer risk assessment, industrial toxicology, pharmacology, behavioral and addiction studies, and neurobiology. Up till recently, the ability of creating genetically modified rats has been limited compared to that in the mouse mainly due to lack of genetic manipulation tools and technologies in the rat. Recent advances in nucleases, such as CRISPR/Cas9 (clustered regularly-interspaced short palindromic repeats/CRISPR associated protein 9), as well as TARGATT™ integrase system enables fast, efficient and site-specific introduction of exogenous genetic elements into the rat genome. Here, we report the generation of a collection of tissue-specific, inducible transgenic Cre rats as tool models using TARGATT™, CRISPR/Cas9 and random transgenic approach. More specifically, we generated Cre driver rat models that allow controlled gene expression or knockout (conditional models) both temporally and spatially through the Cre-ERT2/loxP system. A total of 10 Cre rat lines and one Cre reporter/test line were generated, including eight (8) Cre lines for neural specific and two (2) lines for cardiovascular specific Cre expression. All of these lines have been deposited with the Rat Resource and Research Center and provide a much-needed resource for the bio-medical community who employ rat models for their studies of human diseases.

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The 2.3 kb smooth muscle myosin heavy chain promoter directs gene expression into the vascular system of transgenic mice and rabbits,

Cited by 13 publications

References 30 publications

Leiomodin and tropomodulin in smooth muscle

Leiomodin and tropomodulin in smooth muscle

Cell-Specific Regulatory Modules Control Expression of Genes in Vascular and Visceral Smooth Muscle Tissues

Establishment of a Cre-rat resource for creating conditional and physiological relevant models of human diseases

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