Ckmm-Cre transgenic mice maintain phenotypic and cardiac mitochondrial homeostasis during ketogenic feeding.

Conditional gene targeting using the Cre-loxP system requires validation of each Cre driver line under the specific experimental conditions to be employed, as Cre recombinase expression can cause transgene-associated pathology. The Ckmm-Cre transgenic mouse is widely used for heart- and skeletal muscle-directed conditional gene targeting, yet its phenotypic and cardiac mitochondrial response to ketogenic diet (KD) remains uncharacterized. Here we report that four-week KD feeding did not alter body weight, treadmill endurance, grip strength, locomotor activity, or rotarod performance in young male Ckmm-Cre mice. Cardiac mitochondrial oxygen consumption and hydrogen peroxide production, assessed by high-resolution respirometry, were likewise unchanged. In cardiac tissue lysates, oxidative phosphorylation subunit abundance and VDAC1 levels were maintained, with no major diet-associated changes in mitochondrial protein content. These pilot data establish a baseline reference for future conditional knockout studies employing this Cre driver under ketogenic conditions.