Regulatory role of energy metabolism in skeletal development

To test the consequence of reduced glycolysis and reduced cytoplasimic acetyl-CoA in mouse skeletal development. To reduce glycolysis, Ldha was homozygously deleted in collagen 2 expressing chondrocytes using the Cre-lox sytem [Col2-Cre:Ldha(fl/fl)] on top of one allele germline deletion of Ldhb [Ldhb(+/-)]. To reduce cytoplasmic/nuclear acetyl-CoA, Acly that catalyzes conversion of citrate into acetyl-CoA was deleted in chondrocytes using Col2-Cre. Both mutant mice develop skeletal dysplasia, but former model survive postnatally, whereas Acly mutants die at birth.