PHENOTYPIC ANALYSIS OF MICE EXPRESSING EXCLUSIVELY APOLIPOPROTEIN B48OR APOLIPOPROTEIN B100

Apolipoprotein (apo)-B is found in two farms in mammals: apo-B100, whi ch is made in the liver and the yolk sac, and apo-B48, a truncated pro tein made in the intestine, To provide models for understanding the ph ysiologic purpose for the two forms of apo-B, we used targeted mutagen esis of the apo-B gene to generate mice that synthesize exclusively ap o-B48 (apo-B48-only mice) and mice that synthesize exclusively apo-B10 0 (apo-B100-only mice), Both the apo-B48-only mice and apo-B100-only m ice developed normally, were healthy, and were fertile, Thus, apo-B48 synthesis was sufficient for normal embryonic development, and the syn thesis of apo-B100 in the intestines of adult mice caused no readily a pparent adverse effects on intestinal function or nutrition, Compared with wild-type mice fed a chow diet, the levels of low density lipopro tein (LDL)-cholesterol and very low density lipoprotein- and LDL-triac ylglycerols were lower in apo-B48-only mice and higher in the apo-B100 -only mice, In the setting of apo-E-deficiency, the apo-B100-only muta tion lowered cholesterol levels, consistent with the fact that apo-B10 0-lipoproteins can be cleared from the plasma via the LDL receptor, wh ereas apo-B48-lipoproteins lacking apo-E cannot, The apo-B48-only and apo-B100-only mice should prove to be valuable models for experiments designed to understand the purpose for the two forms of apo-B in mamma lian metabolism.