Mouse hexokinase II gene: structure, cDNA, promoter analysis, and expression pattern

In mammalian tissues, the phosphorylation of intracellular glucose to gluco se-6-phosphate (Glu-6-P) is facilitated by four distinct hexokinase (HK) is oenzymes, designated as HKI-IV. Because of the role of HKII as a leading gl ycolytic enzyme in insulin-sensitive tissues such as skeletal muscle, heart , and adipose tissue, defects in HKII function could contribute to the deve lopment of insulin resistance and perhaps Type 2 diabetes. As a first step towards elucidation of the physiological role of HKII in insulin resistance and type 2 diabetes using mouse knock-out models, we determined the genomi c structure, sequence of the cDNA and of 4.8 kb of the 5' regulatory region , and tissue-specific expression of the mouse HKII gene. The gene comprises 18 exons that span approximately 50 kb of DNA. Nucleotide sequence of the proximal promoter revealed a number of conserved putative transcription fac tor binding motifs. We also found numerous repeat elements throughout the m ouse HKII gene. The mouse HKII cDNA is approximately 5.5 kb in length and c ontains an open reading frome of 2751 bp encoding a protein of 917 amino ac ids. The mouse HKII gene is predominantly expressed in skeletal muscle, hea rt, and adipose tissue. The transcription initiation and polyadenylation si tes for the mouse HKII mRNA were similar to those of the rat and human gene s.