C57BL/6-Tg(tetO-EDN1,-lacZ)9Mhus/J

Stock number: 013729
Research areas: Research Tools

Description

These ET⁺ transgenic mice express the human EDN1 gene and a β-galactosidase (lacZ) reporter, both regulated by the bidirectional tetracycline operator (tetO.

Detailed description

These ET⁺ transgenic mice express the human endothelin (EDN1 or ET-1) gene and a β-galactosidase (lacZ) reporter, both regulated by the bidirectional tetracycline operator, tetO. Homozygous mice are viable, fertile, and normal in size. ET-1 is a vasoconstrictor expressed in endothelial cells, and is a key mediator in vascular tone and renal homeostatsis. When mated to a mutant strain expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), LacZ and ET-1 expression may be regulated with the tetracycline analog doxycycline (DOX) in the double mutant offspring.

When bred to a strain expressing tTA driven by α-myosin heavy chain (α-MHC) cardiomyocyte specific (see Stock No. 003170) overexpression of lacZ and ET-1 results in left ventricular dilation, contractile dysfunction, cardiac enlargement, and widespread inflammation upon removal of DOX. These mice exhibit decreased activity, hunched posture, and labored breathing, resulting in death within days of onset. These mice may be useful as for studying congestive heart failure, and idiopathic dilated cardiomyopathy (DCM).

When bred to a strain expressing tTA in cardiac tissue (Tg(Myh6-tTA)6Smbf, see Stock No. 017770 for example), this mutant mouse strain may be useful in studies of endothelin 1 and inflammation and dilated cardiomyopathy.

Development

The tetO-EDN1 transgene was designed with a bidirectional tetracycline operator (tetO; also called tetracycline-responsive element (TRE, TetRE) or tet-operator), pB_i-1, between two cytomegalovirus (CMV) minimal promoters in opposite orientation. One CMV promoter drives expression of the human endothelin (EDN1 or ET-1) gene, followed by a simian virus 40 (SV40) polyadenylation (polyA) signal, while the other drives expression of a β-galactosidase (lacZ) reporter followed by a β-globin polyA signal. The transgene was microinjected into fertilized C57BL/6 oocytes, and mice from founder line 240i were bred to C57BL/6J mice to establish a colony of ET⁺ mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Tg(tetO-EDN1,-lacZ)9Mhus
Name: transgene insertion 9, Mansoor Husain
MGI accession ID: MGI:4837732
Generation method: Transgenic
Attributes: Reporter; Inducible; Inserted expressed sequence; Humanized sequence
Synonyms: ET-1
Marker symbol: Tg(tetO-EDN1,-lacZ)9Mhus
Marker name: transgene insertion 9, Mansoor Husain
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: EDN1,endothelin 1,human; lacZ,beta-galactosidase,E. coli
Site of expression: When bred to mice expressing a tetracycline transactivator (tTA) or reverse transactivator (rtTA), doxycycline induction results in the expression of lacZ and endothelin (EDN1) in transactivator expressing tissues of the offspring.
Molecular note: The tetO-EDN1 transgene was designed with a bidirectional tetracycline operator (tetO; also called tetracycline-responsive element (TRE, TetRE) or tet-operator), pBi-1, between two cytomegalovirus (CMV) minimal promoters in the opposite orientation. One CMV promoter drives expression of the human endothelin (EDN1 or ET-1) gene, followed by a simian virus 40 (SV40) polyadenylation (polyA) signal, while the other drives expression of a beta-galactosidase (lacZ) reporter followed by a beta-globin polyA signal. Three lines were generated (9, 101, and 403). Line 9 exhibits high levels of expression in the myocardium.