Aldob Conditional Knockout mouse models

Hereditary fructose intolerance is fundamentally a story about Aldob, the mouse ortholog of human ALDOB, whose product is the liver, kidney cortex, and intestinal aldolase isoform distinguished by high catalytic efficiency toward fructose-1-phosphate rather than fructose-1,6-bisphosphate alone. When aldolase B activity fails, ketohexokinase continues phosphorylating dietary fructose, fructose-1-phosphate accumulates, phosphate and adenine nucleotides are sequestered, and hypoglycemia, urate elevation, hepatomegaly, and proximal tubular injury follow. That mechanism makes allele choice sharp: a conditional null answers whether hepatocyte fructolysis drives steatosis and lipogenesis, whereas knockin of a catalytically crippled patient substitution such as A149P reproduces misfolding with residual activity closer to clinical biochemistry. Aldoa and Aldoc cannot substitute, since their fructose-1-phosphate kinetics are poor, so redundancy is not the usual confounder here. Pair Alb-Cre or Villin-Cre with defined fructose challenge protocols and read plasma glucose, hepatic ATP and phosphate, uric acid, and triglyceride flux.

Aldob conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.