Cutaneous
lipids, endogenously synthetized and transported by
lipoproteins, play a pivotal role in maintaining skin barrier. An impairment of extracutaneous
lipid trafficking leads to the development of
xanthomas, mostly arising in hyperlipidemic patients, but also in subjects with
high-density lipoprotein (HDL) deficiency. The aim of this work was to evaluate, in a genetically modified mouse model, lacking two
protein components of HDL particles,
apolipoprotein(
apo)E and
apoA-I, the effect of HDL deficiency on skin morphology. Control mice (C57BL/6),
apoE deficient mice (
EKO),
apoA-I deficient mice (A-IKO) and
apoA-I/
apoE double knockout mice (A-IKO/
EKO) were maintained on a low-fat/low-
cholesterol diet up to 30 weeks of age. At sacrifice, skin biopsies were processed for light (LM) and transmission electron microscopy (TEM). Whereas the skin of
EKO, A-IKO, and C57BL/6 mice was comparable, LM analysis in A-IKO/
EKO mice showed an increase in dermal thickness and the presence of foam cells and T lymphocytes in reticular dermis. TEM analysis revealed the accumulation of
cholesterol clefts in the papillary dermis and of
cholesterol crystals within foam cells. In conclusion, A-IKO/
EKO mice represent an experimental model for investigating the cutaneous phenotype of human HDL deficiency, thus mimicking a condition in which human xanthomatous lesions can develop.