Fig. 2: Hepatic Usp39 knockout impairs liver homeostasis and function.

a Schematic illustrating the generation of the Usp39 conditional knockout mice. The strategy was to insert loxp sites to flank exons 2 of the mouse Usp39 gene. Usp39^fl/fl mice were crossed with albumin-Cre mice to generate Usp39-HKO mice. b Immunoblotting was performed to determine Usp39 knockout efficiency using liver tissues and primary hepatocytes (n = 3 independent experiments). Band intensities were quantified by Image J. c Body weight of male mice was recorded from 1 to 16 weeks after birth (n = 5 per group). d Representative images of 5-week-old control and Usp39-HKO male mice. e–g Body weight, liver weight, and liver/body weight ratio were compared between control and Usp39-HKO mice (n = 10 per group). h H&E staining (n = 6), IHC staining of Pcna (n = 15) and Ki67 (n = 10) in the liver sections of 5-week-old male mice. Red arrows indicate Ki67-positive nuclei. Scale bars, 50 µm. i The Pcna-positive cells count of 5-week-old male mice liver sections (n = 15). j The Ki67-positive cells count of 5-week-old control (n = 11) and Usp39-HKO (n = 10) male mice liver sections. k–m Relative mRNA expression Afp (n = 4), H19 (n = 4), and Alb (n = 3) in the liver of 5-week-old male mice. n Serum ALT, AST, LDH and albumin levels were measured in 5-week-old male mice fasted for 16 h (n  =  20 per group). o IHC staining of F4/80, Sirius Red staining in the liver sections of 5- and 10-week-old male mice (n = 5 per group). Scale bars, 50 µm. p qPCR was performed to analyze mRNA expression indicated genes in livers of 5-week-old male mice (n = 4 per group). Images are representative of at least three independent experiments. The p-value was obtained by unpaired two-sided Student’s t-test, and the results are presented as the mean ± S.D. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.  NS, stands for non-significant. Alb, albumin. Afp, α-Fetoprotein. MW, molecular weight. Source data are provided as a Source data file.