Thyroid hormone receptor sumoylation modulates preadipocyte proliferation and white adipose tissure stores

We generated sumoylation -defective mouse model carrying double mutation at mouse Thra gene, resulting in amino acids change at TRHA K283Q and K288R. We found that THRA K283/K288R (mutant) mouse has significant reducution in white adipose stores and 50% less serum leptin, compared to WT mice. The mechanims reduction in fat store is in part due to the mutant disrupts the adipocytes proliferation through delaying G1/S transition, which is the consequences of THRA mutant interfers with CREB-mediated gene expression of the cell cycle regulators, CCNA1, CCND2, Cdk2 and Cuin3. Overall design: Global knockin generates mutation in mouse Thra gene, which produced THRA K283Q/K288R mutation. Comparing WT and mutant mice fat content ad fat stem cells proliferation.