Idh1 Conditional Knockout mouse models

Cytosolic isocitrate dehydrogenase 1, encoded by Idh1 and orthologous to human IDH1, catalyzes the NADP-dependent oxidative decarboxylation of isocitrate to alpha-ketoglutarate in the cytoplasm and peroxisomes, supplying reducing equivalents for lipid synthesis and oxidative defense. Tumor alleles are heterozygous missense substitutions at arginine 132, most often R132H, which convert the enzyme into a neomorph that further reduces alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. Accumulated D-2HG competitively inhibits alpha-ketoglutarate dependent dioxygenases including TET2, the KDM4 and KDM6 demethylases, and prolyl hydroxylases, producing the CpG island hypermethylator phenotype and differentiation block characteristic of low grade glioma, chondrosarcoma, cholangiocarcinoma, and acute myeloid leukemia. Because the retained wild type allele is mechanistically required, the correct model is a conditional Lox-Stop-Lox R132H knockin at the endogenous locus rather than a null. Match Cre timing and lineage to the tumor type and use D-2HG suppression as the pharmacodynamic endpoint.

Idh1 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.