These inducible PLM S68E transgenic mice express mutant dog Fxyd1, FXYD domain-containing ion transport regulator 1 (or phospholemman), under the direction of a modified mouse alpha-myosin heavy chain minimal promoter (Myh6) fused with a tetracycline operator promoter (tetO). Phosphlemman (or FXYD1) is member of the FXYD family of small ion transport regulators. The phosphlemman (or FXYD1) S68E mutation blocks serine phosphorylation and inhibits the ion transporter SLC8A1 (or NCX1), but does not inhibit Na+-K+-ATPase activity.



Mice hemizygous for the transgenic insert are viable and fertile. It is not known if homozygotes are viable.

When mated to mice carrying MHC-tTA (also known as Tg(Myh6-tTA)55Rbns), SLC8A1*S68E expression is directed to cardiac myocytes and regulated with tetracycline or its analog doxycycline (DOX). Following DOX induction, bitransgenic mice exhibit ventricular arrhythmias, bradycardia, increased left ventricular mass, decreased cardiac output, alterations in Ca²⁺ and Na⁺ regulation and increased mortality (50%) due to heart failure. This strain may be useful for studying phosphlemman as a therapeutic target in ischemic heart disease.