<i>Hprt</i>-targeted transgenes provide new insights into smooth muscle-restricted promoter activity

Touw, Ketrija; Hoggatt, April M.; Simon, Gina; Herring, B. Paul

doi:10.1152/ajpcell.00445.2006

Cited by 10 publications

(8 citation statements)

References 36 publications

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“…We have previously shown that a CArG element within the telokin promoter is also critical for expression of telokin transcripts through analysis of transgenic reporter mice and targeting the endogenous telokin promoter (34,42). Together with the current findings, these data show that SRF plays a key role in regulating expression of multiple transcripts from the mylk1 gene.…”

Section: Volume 288 • Number 48 • November 29 2013supporting

confidence: 81%

“…I CArG -smMLCK(Ϫ389/ϩ8427) pWhere and ⌬I CArG -smMLCK(Ϫ389/ϩ8427) pWhere plasmids were linearized and microinjected into pronuclei of fertilized oocytes by standard procedures by the Indiana University School of Medicine transgenic mouse facility. Neonatal founder mice were genotyped for the presence of the transgene and were analyzed at 1 month old by ␤-galactosidase staining as described previously (34). All animal experiments were conducted under the approval of the Indiana University School of Medicine Institutional Animal Care and Use Committee.…”

Section: Generation Of Targeting Vector For Homologous Recombination-mentioning

confidence: 99%

“…This may simply reflect the sensitivity of lacZ detection or the nonnative chromatin environment of reporter transgenes. Although the transgenic reporter mice were generated using a pWhere lacZ expression vector that is CpG-free and has H19 insulator elements flanking the transgene, we have previously shown that the telokin promoter also does not drive high levels of expression in many founder mice generated using this transgene vector (34). Because the promoter and regulatory elements analyzed are embedded within introns of the larger mylk1 gene, it is possible that transcription from the promoters that drive expression of the 220-kDa MLCK may modulate the chromatin structure of the gene to facilitate the activity of these internal elements.…”

Section: Volume 288 • Number 48 • November 29 2013mentioning

confidence: 99%

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Regulation of 130-kDa Smooth Muscle Myosin Light Chain Kinase Expression by an Intronic CArG Element

Chen¹,

Zhang

et al. 2013

Journal of Biological Chemistry

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Background: Mechanisms regulating transcription of MLCK are poorly defined. Results: Deleting a CArG element from the mylk1 gene specifically decreased expression of the 130-kDa smMLCK isoform, resulting in decreased intestinal contractility and proliferation. Conclusion: The 130-kDa smMLCK isoform has functions that cannot be compensated for by the 220-kDa MLCK. Significance: Floxed mylk1 mice permit specific functions of the 130-kDa smMLCK to be determined.

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Section: Volume 288 • Number 48 • November 29 2013supporting

confidence: 81%

Section: Generation Of Targeting Vector For Homologous Recombination-mentioning

confidence: 99%

Section: Volume 288 • Number 48 • November 29 2013mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of 130-kDa Smooth Muscle Myosin Light Chain Kinase Expression by an Intronic CArG Element

Chen¹,

Zhang

et al. 2013

Journal of Biological Chemistry

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“…This site, upstream of a functional HPRT gene, was chosen for its ability to give reliable transgene expression (Bronson et al, 1996; Cvetkovic et al, 2000; Portales-Casamar et al, 2010; Touw et al, 2007). The integration places this gDNA into a dox-inducible locus regulated by a second generation, tight, tet-response element (Agha-Mohammadi et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Dominant Lethal Pathologies in Male Mice Engineered to Contain an X-Linked DUX4 Transgene

et al. 2014

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SUMMARY Facioscapulohumeral muscular dystrophy (FSHD) is an enigmatic disease associated with epigenetic alterations in the subtelomeric heterochromatin of the D4Z4 macrosatellite repeat. Each repeat unit encodes DUX4, a gene that is normally silent in most tissues. Besides muscular loss, most patients suffer retinal vascular telangiectasias. To generate an animal model, we introduced a doxycycline-inducible transgene encoding DUX4and 3′genomic DNA into a euchromatic region of the mouse X chromosome. Without induction, DUX4 RNA was expressed at low levels in many tissues and animals displayed a variety of unexpected dominant leaky phenotypes, including male-specific lethality. Remarkably, rare live-born males expressed DUX4 RNA in the retina and presented a retinal vascular telangiectasia. By using doxycycline to induce DUX4 expression in satellite cells, we observed impaired myogenesis in vitro and in vivo. This mouse model, which shows pathologies due to FSHD-related D4Z4 sequences, is likely to be useful for testing anti-DUX4 therapies in FSHD.

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“…␤-Galactosidase staining, immunofluorescence, and hematoxylin-eosin (H&E) staining were performed as reported previously (28). For immunofluorescence analysis, the primary antibodies used were Brg1 (SC-17796 [Santa Cruz]; 1:100), SM1 and SM2 (15), telokin/myosin light-chain kinase (MLCK) (10), cleaved caspase 3 (Cell Signaling; 1:50), Ki67 (M7249 [Dako]; 1:25), and SM ␣-actin (Sigma; 1:500).…”

Section: Methodsmentioning

confidence: 99%

SWI/SNF Complexes Containing Brahma or Brahma-Related Gene 1 Play Distinct Roles in Smooth Muscle Development

Zhang

Chen

Kim

et al. 2011

Molecular and Cellular Biology

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SWI/SNF ATP-dependent chromatin-remodeling complexes containing either Brahma-related gene 1 (Brg1) or Brahma (Brm) play important roles in mammalian development. In this study we examined the roles of Brg1 and Brm in smooth muscle development, in vivo, through generation and analysis of mice harboring a smooth muscle-specific knockout of Brg1 on wild-type and Brm null backgrounds. Knockout of Brg1 from smooth muscle in Brg1 flox/flox mice expressing Cre recombinase under the control of the smooth muscle myosin heavy-chain promoter resulted in cardiopulmonary defects, including patent ductus arteriosus, in 30 to 40% of the mice. Surviving knockout mice exhibited decreased expression of smooth muscle-specific contractile proteins in the gastrointestinal tract, impaired contractility, shortened intestines, disorganized smooth muscle cells, and an increase in apoptosis of intestinal smooth muscle cells. Although Brm knockout mice had normal intestinal structure and function, knockout of Brg1 on a Brm null background exacerbated the effects of knockout of Brg1 alone, resulting in an increase in neonatal lethality. These data show that Brg1 and Brm play critical roles in regulating development of smooth muscle and that Brg1 has specific functions within vascular and gastrointestinal smooth muscle that cannot be performed by Brm.The SWI/SNF complex is perhaps the best-characterized mammalian ATP-dependent chromatin-remodeling complex (8). It is comprised of 7 to 11 components, which assemble into distinct complexes containing either Brahma-related gene 1 (Brg1) or Brahma (Brm) ATPase subunits. Brg1 and Brm are ubiquitously expressed in almost all tissues. Studies have suggested that Brg1 and Brm can have either redundant or distinct roles in regulating gene expression. For example, although Brg1 but not Brm has been shown to interact with Crp2 and subsequently induce expression of smooth muscle (SM)-specific genes (4), either Brg1 or Brm has been shown to be sufficient to support the smooth muscle myogenic activity of the myocardin family of activators in SW13 cells (33,34). Data from knockout mice suggest that Brg1-and Brm-containing SWI/SNF complexes are functionally distinct in vivo. Brg1 knockout mice die early in embryonic development during the periimplantation stage (1), while global Brm knockout mice develop normally. On a 129/sv background but not a mixed 129/sv ϫ C57BL/6 background, adult Brm knockout mice exhibited a higher body weight than wild-type (WT) littermates (24).To circumvent the embryonic lethality observed in Brg1 knockout mice, several groups have generated and analyzed tissue-specific Brg1 knockout mice. These studies have revealed unique roles for Brg1-containing SWI/SNF complexes in development of many tissues (5, 11-13, 16, 20, 26). However, few of these studies have determined if Brm also contributes to these developmental pathways. One study combined a tissuespecific Brg1 knockout with a global Brm knockout to show that further loss of Brm did not exacerbate the erythropoietic or endothel...

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Hprt-targeted transgenes provide new insights into smooth muscle-restricted promoter activity

Abstract: Touw K, Hoggatt AM, Simon G, Herring BP. Hprt-targeted transgenes provide new insights into smooth muscle-restricted promoter activity.

Cited by 10 publications

References 36 publications

Regulation of 130-kDa Smooth Muscle Myosin Light Chain Kinase Expression by an Intronic CArG Element

Regulation of 130-kDa Smooth Muscle Myosin Light Chain Kinase Expression by an Intronic CArG Element

Dominant Lethal Pathologies in Male Mice Engineered to Contain an X-Linked DUX4 Transgene

SWI/SNF Complexes Containing Brahma or Brahma-Related Gene 1 Play Distinct Roles in Smooth Muscle Development

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