Fbp1 Knockout mouse models

Fbp1 encodes the mouse ortholog of human FBP1, the liver and kidney fructose-1,6-bisphosphatase that hydrolyzes fructose-1,6-bisphosphate to fructose-6-phosphate and, with Pck1 and G6pc1, sets gluconeogenic flux. The tetrameric enzyme is allosterically inhibited by AMP at a site distinct from the active site and synergistically by fructose-2,6-bisphosphate, making it the node where cellular energy charge and insulin signaling veto hepatic glucose output. Human FBP1 deficiency presents as fasting hypoglycemia with lactic acidosis and ketosis, typically unmasked by intercurrent illness rather than at baseline. Allele planning follows that logic: a hepatocyte conditional null with Alb-Cre interrogates fasting glucose production directly, AMP-site mutant knockins create a constitutively active enzyme to probe flux control, and humanization supports variant and inhibitor studies. Because Fbp2 covers skeletal muscle, a liver-restricted null leaves systemic FBPase activity intact. Pair alleles with fasting and pyruvate tolerance testing plus glycerol tracing rather than steady-state glycemia alone.

Whole body loss of Fbp1 gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.