Construction of Pnpla3 I148M and Tm6sf2 E167K double mutant mouse model / 临床肝胆病杂志

ABSTRACT

Objective To construct a Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model by crossbreeding Pnpla3 148M/M homozygous mice and Tm6sf2 167K/K homozygous mice. Methods Pnpla3 148I/M Tm6sf2 167E/K heterozygous mice were bred by hybridization of Pnpla3 148M/M Tm6sf2 167E/E and Pnpla3 148I/I Tm6sf2 167K/K homozygous mice, and the Pnpla3 148M/M Tm6sf2 167K/K mice were obtained by the self-crossbreeding of Pnpla3 148I/M Tm6sf2 167E/K mice. Male mice of Pnpla3 148M/M Tm6sf2 167K/K ( n =6), Pnpla3 148M/M Tm6sf2 167E/E ( n =6), and Pnpla3 148I/I Tm6sf2 167K/K ( n =6) genotypes and Wt mice ( n =6) were fed with normal diet for 8 weeks, and then the glucose and lipid metabolism indices were measured. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison bewteen two groups. Results Agarose gel electrophoresis and nucleic acid sequencing results showed that the Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model was successfully constructed. There were no significant difference in body weight between the Pnpla3 148M/M Tm6sf2 167K/K mice and the Pnpla3 148M/M Tm6sf2 167E/E , Pnpla3 148I/I Tm6sf2 167K/K , and Wt mice (all P > 0.05). The Pnpla3 148M/M Tm6sf2 167K/K mice had a significantly higher liver wet weight than the Wt mice ( P 0.05). Also, there were no significant differences in the serum levels of biochemical indices between the Pnpla3 148M/M Tm6sf2 167K/K mice and the Pnpla3 148M/M Tm6sf2 167E/E , Pnpla3 148I/I Tm6sf2 167K/K , and Wt mice (all P > 0.05). Oil red O staining of the liver showed that more lipid accumulation was observed in the Pnpla3 148M/M Tm6sf2 167K/K mice than in the Pnpla3 148M/M Tm6sf2 167E/E and Wt mice. Conclusion The Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model was successfully constructed. Pnpla3 Ⅰ 148M and Tm6sf2 E 167K double mutations can cause abnormal glucose metabolism in mice.