BioProject

We observed that Ildr2 knockdown via adenovirally-delivered shRNA (Adv-Ildr2 shRNA) causes hepatic steatosis in mice. More...

We observed that Ildr2 knockdown via adenovirally-delivered shRNA (Adv-Ildr2 shRNA) causes hepatic steatosis in mice. Acute, liver-specific Ildr2 knockout mice generated by infecting C57BL/6J mice segregating for a floxed allele of Ildr2 with adenoviral Cre recombinase (Adv-Cre) do not develop hepatic steatosis. However, administration of Adv-Ildr2 shRNA to Ildr2 knockout mice (Ildr2floxed; albumin-cre) did cause hepatic steatosis, indicating that the Adv-Ildr2 shRNA had apparent “off-target” effects on gene(s) other than Ildr2. To determine additional targets of Ildr2 shRNA that may regulate hepatic lipid metabolism, we performed RNA sequencing on liver samples from (1) Adv-Ildr2 shRNA knockdown mice, (2) Adv-lacZ shRNA control mice, and (3) Adv-Cre Ildr2 knockout mice. For the purposes of our study, we sought to identify genes downregulated by Adv-Ildr2 shRNA, but unchanged in Adv-lacZ shRNA control or Adv-Cre Ildr2 knockout mice. The hepatic steatosis observed in Adv-Ildr2 shRNA knockdown mice was likely due to shRNA targeting of other “off-target” genes. We propose that the genes candidates identified in this sequencing experiment may lead to identification of novel regulators of hepatic lipid metabolism. Overall design: Liver tissue from male, BL6 mice, 10 wks old. Adv-lacZ shRNA (n=4), Adv-Ildr2 shRNA (n=4), Adv-cre (n=4) Submitter indicates the raw data files are no longer available. Less...