High-density lipoprotein deficiency in genetically modified mice deeply affects skin morphology: A structural and ultrastructural study.

Abstract

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.

• Authors: Francesca Arnaboldi, Marco Busnelli, Laura Cornaghi, Stefano Manzini, Cinzia Parolini, Federica Dellera, Giulia Sara Ganzetti, Cesare Riccardo Sirtori, Elena Donetti, Giulia Chiesa
• Journal: Experimental cell research (Exp Cell Res) Vol. 338 Issue 1 Pg. 105-12 (Oct 15 2015) ISSN: 1090-2422 [Electronic] United States
• PMID: 26241937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Apolipoprotein A-I
• Apolipoproteins E

Topics

• Animals
• Apolipoprotein A-I (genetics)
• Apolipoproteins E (genetics)
• Hypoalphalipoproteinemias (pathology)
• Mice, Inbred C57BL
• Mice, Knockout
• Skin (pathology)
• Xanthomatosis (genetics, pathology)