Muscle disease caused by mutations in the skeletal muscle alpha-actin gene (ACTA1)

We have generated transgenic mouse lines that carry the promoter region of the chicken skeletal muscle alpha (alpha sk) actin gene linked to the bacterial chloramphenicol acetyltransferase (CAT) gene. In adult mice, the pattern of transgene expression resembled that of the endogenous alpha sk actin gene. In most of the transgenic lines, high levels of CAT activity were detected in striated muscle (skeletal and cardiac) but not in the other tissues tested. In striated muscle, transcription of the transgene was initiated at the normal transcriptional start site of the chicken alpha sk actin gene. The region from nucleotides -191 to +27 of the chicken alpha sk actin gene was sufficient to direct the expression of CAT in striated muscle of transgenic mice. These observations suggest that the mechanism of tissue-specific actin gene expression is well conserved in higher vertebrate species.

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The chicken skeletal muscle alpha-actin promoter is tissue specific in transgenic mice.

Molecular and Cellular Biology ◽

10.1128/mcb.9.9.3785 ◽

1989 ◽

Vol 9 (9) ◽

pp. 3785-3792 ◽

Cited By ~ 36

Author(s):

C J Petropoulos ◽

M P Rosenberg ◽

N A Jenkins ◽

N G Copeland ◽

S H Hughes

Keyword(s):

Skeletal Muscle ◽

Transgenic Mice ◽

Striated Muscle ◽

Transcriptional Start Site ◽

Actin Gene ◽

Tissue Specific ◽

Adult Mice ◽

Transgenic Lines ◽

Alpha Actin ◽

Chicken Skeletal Muscle

We have generated transgenic mouse lines that carry the promoter region of the chicken skeletal muscle alpha (alpha sk) actin gene linked to the bacterial chloramphenicol acetyltransferase (CAT) gene. In adult mice, the pattern of transgene expression resembled that of the endogenous alpha sk actin gene. In most of the transgenic lines, high levels of CAT activity were detected in striated muscle (skeletal and cardiac) but not in the other tissues tested. In striated muscle, transcription of the transgene was initiated at the normal transcriptional start site of the chicken alpha sk actin gene. The region from nucleotides -191 to +27 of the chicken alpha sk actin gene was sufficient to direct the expression of CAT in striated muscle of transgenic mice. These observations suggest that the mechanism of tissue-specific actin gene expression is well conserved in higher vertebrate species.

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GGeneration of an efficient artificial promoter of bovine skeletal muscle alpha-actin gene (ACTA1) through addition of cis-acting element

Cellular & Molecular Biology Letters ◽

10.1515/cmble-2015-0009 ◽

2015 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Qian Hu ◽

Huili Tong ◽

Dandan Zhao ◽

Yunkao Cao ◽

Weiwei Zhang ◽

...

Keyword(s):

Skeletal Muscle ◽

Core Promoter ◽

Genetically Engineered ◽

Actin Gene ◽

Base Pairs ◽

Cis Acting ◽

The Core ◽

Binding Factor ◽

Bovine Skeletal Muscle ◽

Alpha Actin

AbstractThe promoter of skeletal muscle α-actin gene (ACTA1) is highly muscle specific. The core of the bovine ACTA1 promoter extends from +29 to −233, about 262 base pairs (bp), which is sufficient to activate transcription in bovine muscle satellite cells. In this study, analysis by PCR site-specific mutagenesis showed that the cis-acting element SRE (serum response element binding factor) was processed as a transcriptional activator. In order to enhance the bovine ACTA1 promoter’s activity, we used a strategy to modify it. We cloned a fragment containing three SREs from the promoter of ACTA1, and then one or two clones were linked upstream of the core promoter (262 bp) of ACTA1. One and two clones increased the activity of the ACTA1 promoter 3-fold and 10-fold, respectively, and maintained muscle tissue specificity. The modified promoter with two clones could increase the level of ACTA1 mRNA and protein 4-fold and 1.1-fold, respectively. Immunofluorescence results showed that green fluorescence of ACTA1 increased. Additionally, the number of total muscle microfilaments increased. These genetically engineered promoters might be useful for regulating gene expression in muscle cells and improving muscle mass in livestock.

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