Generation of mice with a conditional allele for G6pc.

Glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC) catalyzes the hydrolysis of glucose-6-phosphate to glucose and is a key enzyme in interprandial glucose homeostasis. Mutations in the human G6PC gene, expressed primarily in the liver, kidney, and intestine, cause glycogen storage disease Type Ia (GSD-Ia), an autosomal recessive disorder characterized by a disturbed glucose homeostasis. For better understanding of the roles of G6Pase-alpha in different tissues and in pathological conditions, we have generated mice harboring a conditional null allele for G6pc by flanking Exon 3 of the G6pc gene with loxP sites. We confirmed the null phenotype by using the EIIa-Cre transgenic approach to generate mice lacking Exon 3 of the G6pc gene. The resulting homozygous Cre-recombined null mice manifest a phenotype mimicking G6Pase-alpha-deficient mice and human GSD-Ia patients. This G6pc conditional null allele will be valuable to examine the consequence of tissue-specific G6Pase-alpha deficiency and the mechanisms of long-term complications in GSD-Ia.