Researchers can manipulate the genes of a mouse so that a single gene in a single tissue either produces an inactive protein (a knockout mouse) or produces a protein that is always (constitutively) active. What effects on metabolism would you predict for mice with the following genetic changes?

Knockout of the FBPase-2 domain of PFK-2/FBPase-2 in the liver:

1) Effect on glucose metabolism:
2) Effect on glucose levels:

Constitutively active PFK-2 in the liver:

1) Effect on glucose metabolism:
2) Effect on glucose levels:

Fructose-2,6-bisphosphate (F2,6P) activates the key glycolysis enzyme, phosphofructokinase (PFK) and inhibits fructose bisphosphate phosphatase in gluconeogenesis. F2,6P is synthesized by phosphofructokinase-2 (PFK-2) and broken down by fructose-bisphosphatase-2 (FBPase-2). Both PFK-2 and FBPase-2 are found in the liver. PFK-2 is activated by insulin in response to high glucose levels. FBPase-2 activity in increased by glucagon when glucose needs to be metabolized.

Explanation: