Heterozygous Kctd5 knockout mice exhibit abnormal lipid metabolism.

The KCTD gene family is conserved across species, yet the knowledge of its function is limited. Recently, increasing studies focused on KCTD5 emerged. The functions of KCTD5 and its associations with various diseases were revealed. However, the function of KCTD5 in vivo has remained elusive. We generated Kctd5+/- mice with the Kctd5 gene's exon 2 deleted using CRISPR/Cas9 technology. Breeding experiments on Kctd5+/- mice showed that only Kctd5+/- and Kctd5+/+ mice could be born normally, while Kctd5-/- embryos died in early embryonic development. Compared to Kctd5+/+ mice, Kctd5+/- mice have a shorter lifespan and exhibit spleen enlargement, abnormal blood cell counts, and metabolic disorders, including elevated cholesterol and triglyceride levels. Genome-wide gene expression analysis revealed that KCTD5 may affect the PPAR signaling pathway and subsequent the expression of Apo family genes, thereby regulating lipid metabolism. In summary, our study identified a previously unrecognized role of KCTD5 in regulating lipid metabolism and KCTD5 deficiency-induced animal phenotype, and revealed multiple correlations between KCTD5 and various molecules in mice.