Functional loss of ABCA1 in mice causes severe placental malformation, aberrant lipid distribution, and kidney glomerulonephritis as well as high-density lipoprotein cholesterol deficiency

Tangier disease (TD) and familial HDL deficiency (FHA) have recently been l inked to mutations in the human ATP-binding cassette transporter 1 (hABCA1) , a member of the ABC superfamily, Both diseases are characterized by the l owering or lack of high-density lipoprotein cholesterol (HDL-C) and low ser um cholesterol. The murine ABCA1-/- phenotype corroborates the human TD Lin kage to ABCA1, Similar to TD in humans, HDL-C is virtually absent in ABCA1- /- mice accompanied by a reduction in serum cholesterol and lipid depositio n in various tissues. in addition, the placenta of ABCA1-/- mice is malform ed, resulting in severe embryo growth retardation, fetal loss, and neonatal death. The basis for these defects appears to be altered steroidogenesis, a direct result of the lack of HDL-C. By 6 months of age, ABCA1-/- animals develop membranoproliferative glomerulonephritis due to deposition of immun ocomplexes followed by cardiomegaly with ventricular dilation and hypertrop hy, ultimately succumbing to congestive heart failure. This murine model of TD mill be very useful in the study of lipid metabolism, renal inflammatio n, and cardiovascular disease and may reveal previously unsuspected relatio nships between them.