NDLI: A 7.1 kbp beta-myosin heavy chain promoter, efficient for green fluorescent protein expression, probably induces lethality when overexpressing a mutated transforming growth factor-beta type II receptor in transgenic mice

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A 7.1 kbp beta-myosin heavy chain promoter, efficient for green fluorescent protein expression, probably induces lethality when overexpressing a mutated transforming growth factor-beta type II receptor in transgenic mice

Content Provider	Springer Nature Link
Author	Allegra, Séverine Bouazza, Lamia Benetollo, Claire Yuan Li, Jacques Langlois, Dominique
Copyright Year	2005
Abstract	The roles of transforming growth factor-beta (TGFβ) in heart or skeletal muscle development and physiology are still the subject of controversies. Our aim was to block, in transgenic mice, the TGFβ signalling pathway by a dominant negative mutant of the TGFβ type II receptor fused to the enhanced green fluorescent protein (TβRII-KR-EGFP) under the control of a 7.1 kbp mouse beta-myosin heavy chain (βMHC) promoter to investigate the roles of TGFβ in the heart and slow skeletal muscles. First, we generated two transgenic lines overexpressing EGFP under the control of the 7.1 kbp βMHC promoter. In embryos, EGFP was detectable as early as 7.5 days post coitum. In embryos, newborns and adults, EGFP was expressed mainly in the cardiac ventricles and in slow skeletal muscles. EGFP expression was intense in the bladder but weak in the intestines. In contrast to the endogenous βMHC promoter, the activity of the 7.1 kbp βMHC promoter in the transgene was not repressed after birth and remained high in adult transgenic mice. We obtained two founders with the transgene comprising the TβRII-KR-EGFP sequence under the control of the 7.1 kbp βMHC promoter. These founders were generated at a very low frequency and expressed barely detectable levels of TβRII-KR-EGFP mRNA. Our failure to obtain transgenic lines overexpressing the dominant negative receptor suggests that the blocking of the TGFβ signalling pathway in the heart and slow skeletal muscles could be embryonically lethal. To conclude, the 7.1 kbp βMHC promoter directs high levels of transgene expression in the cardiac ventricles and in slow skeletal muscles of the mouse. Analysis of the consequences of the blocking of the TGFβ signalling pathway in the heart will require the use of tissue specific means of conditional gene invalidation.
Starting Page	69
Ending Page	80
Page Count	12
File Format	PDF
ISSN	09628819
Journal	Transgenic Research
Volume Number	14
Issue Number	1
e-ISSN	15739368
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2005-01-01
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	dominant negative TGFβ type II receptor EGFP reporter gene mouse beta-myosin heavy chain promoter tissue-specific expression transgenic mice Human Genetics Plant Sciences Plant Genetics & Genomics Animal Genetics and Genomics
Content Type	Text
Resource Type	Article
Subject	Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science

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