Gk^lox mice may be used to generate cell specific knock-outs of glucokinase, depending which cre-expressing transgenic mouse is used.  In humans, glucokinase gene mutations cause maturity onset diabetes of the young (MODY-GK), a disease that is characterized by early onset and persistent hyperglycemia. Thus, these mice are useful in determining how diminished experssion of glucokinase in specific cells causes hyperglycemia.

A gene targeting strategy was used to flank exons 9 and 10 in the glucokinase gene with two tandomly-oriented loxP sites. This strain allows for the tissue specific knock-out of glucokinase to be made. For example, crossing the gk^lox/lox mice with an insulin-cre transgenic mouse generates a beta cell specific knock-out of glucokinase. Genotype by DNA PCR using primers 5'-TGT CTC AAT TTG CTG TGT CCT CCA-3' and 5'-TCT GTT AAT GCA AAT GCT CGT GTT-3'. A 710 bp band will be amplified for the gk^lox allele and a 605 bp band for the wild type allele. Homozygous gk^lox/lox mice are viable but have a blood glucose concentrations slightly higher than wild types (194 +/- 3 mg/dl vs. 175 +/- 8 mg/dl). This finding suggests that the insertion of a loxP site (and some flanking sequences) between exons 8 and 9 may have caused a slight attenuation in glucokinase gene expression compared to mice with two wild type alleles.

After achieving germline transmission mice carrying the gk^lox allele were backcrossed for ten generations into a C57Bl/6J background.