Hk2 Conditional Knockout mouse models

Hk2 is the mouse ortholog of human HK2 and encodes the inducible hexokinase of skeletal muscle, heart and adipose tissue, distinguished by two catalytically active halves and by transcriptional induction downstream of insulin, hypoxia through HIF1A, and MYC, which together scale glycolytic entry to demand. Like HK1 it binds VDAC at the outer mitochondrial membrane, an interaction promoted by AKT-dependent phosphorylation that both accelerates glucose phosphorylation and suppresses BAX-dependent apoptosis, giving the protein a survival function alongside catalysis. Tumors frequently depend on this isoform, and Hk2 deletion slows initiation and progression in several models while leaving normal tissues comparatively intact. A conditional null with muscle, adipose or tumor-restricted Cre addresses insulin-stimulated glucose disposal and tumor glycolytic dependence, whereas mitochondrial binding mutant knockins isolate the antiapoptotic role. Since Hk1 remains active in the same tissues, quantify total hexokinase activity, and match allele to clamp studies, fluorodeoxyglucose imaging, or tumor latency endpoints.

Tissue restricted knockout of Hk2 keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.