Ribonucleic acid efflux from isolated mouse liver nuclei is altered by diet and genotypically determined change in...

Differences in immunological abnormalities like autoimmunity, abnormal T cell proliferative disorders and accelerated ageing occur between MRL/Mp-lpr/lpr(lpr/lpr) and MRL/Mp-+/+(+/+) mice as a consequence of one gene. The present study was designed to assess the effect of these differences in genotype and diet on the composition and function of the liver nuclear envelope. Mice of both strains were fed nutritionally adequate diets differing only in fatty acid composition for 4 weeks. Phospholipid fatty acid composition of the liver nuclear envelope was determined and the effect of altering the lipid composition of the nuclear membrane on nucleoside-triphosphatase (NTPase) activity, ribonucleic acid (RNA) efflux and binding of L-triiodothyronine (L-T3) was determined. Strain of mouse and level of dietary linoleic acid exhibited significant effects on the phospholipid fatty acid composition of the nuclear envelope. Levels of 18:1(n - 9) and 18:2(n - 6) were lower and 20:4(n - 6) content was higher in nuclear envelope phospholipids of lpr/lpr mice compared with mice of the +/+ strain. Mice fed the high linoleic acid diet exhibited higher levels of 18:0, 18:2(n - 6) and 20:4(n - 6) and lower levels of 16:0 and 18:1(n - 9) in liver nuclear envelope phospholipids, compared with mice fed the low linoleic acid diet. These changes in membrane composition were reflected in alteration of NTPase activity and efflux of RNA from isolated mouse liver nuclei. Nucleoside triphosphatase activity and efflux of ribonucleic acid from isolated nuclei were significantly higher in livers of the lpr/lpr strain. NTPase activity and RNA efflux from isolated nuclei were higher in the high linoleic acid fed group compared with the low linoleic acid group. A single class of binding sites for L-T3 was present in liver nuclear envelopes of these mice and Kd values were not influenced by strain or dietary linoleic acid levels. Nuclear envelopes prepared from +/+ animals exhibited a significantly higher number of binding sites for L-T3 compared with the lpr/lpr group. These observations indicate that the single gene difference characterizing lpr/lpr mice from +/+ mice results in alterations in the composition and function of the nuclear envelope. This genetic difference also alters the response of this membrane to dietary factors known to modulate characteristics and functions of the nuclear envelope.