G6pc Conditional Knockout mouse models

Encoding the catalytic subunit of glucose-6-phosphatase, G6pc is the mouse ortholog of human G6PC and completes both gluconeogenesis and glycogenolysis by hydrolyzing glucose-6-phosphate within the endoplasmic reticulum lumen, working obligately with the Slc37a4 transporter that delivers substrate across the membrane. Loss-of-function mutations cause glycogen storage disease type Ia, with fasting hypoglycemia, hepatomegaly, lactic acidemia, and nephropathy, and whole-body nulls in mouse suffer severe neonatal hypoglycemia and high early mortality, so survivable studies generally require a floxed allele deleted postnatally in liver or kidney using Alb-Cre or AAV8-delivered Cre. Patient-mutation knockins such as R83C preserve residual biology for enzyme-correction studies, whereas humanization of the locus is the design that supports gene therapy, base editing, and mRNA replacement testing against the actual human sequence. Note that G6pc2 and G6pc3 do not substitute for hepatic output, so redundancy is not a rescue here; match allele and Cre timing to the metabolic endpoint you intend to measure.

Conditional deletion of G6pc limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to G6pc floxed stock yields usable cohorts.