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

• Published in: Experimental cell research Vol. 338; no. 1; pp. 105 - 112
• Main Authors: Arnaboldi, Francesca, Busnelli, Marco, Cornaghi, Laura, Manzini, Stefano, Parolini, Cinzia, Dellera, Federica, Ganzetti, Giulia Sara, Sirtori, Cesare Riccardo, Donetti, Elena, Chiesa, Giulia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2015; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Apolipoprotein A-I - genetics; APOLIPOPROTEINS; Apolipoproteins E - genetics; BIOPSY; CHOLESTEROL; Cholesterol clefts; DIET; FATS; HDLs; Hypoalphalipoproteinemias - pathology; LYMPHOCYTES; MICE; Mice, Inbred C57BL; Mice, Knockout; MORPHOLOGY; PATIENTS; PHENOTYPE; SKIN; Skin - pathology; THICKNESS; TRANSMISSION ELECTRON MICROSCOPY; VISIBLE RADIATION; Xanthomatosis - genetics; Xanthomatosis - pathology; HDLs; Transmission electron microscopy; Apolipoproteins; Cholesterol clefts
• ISSN: 0014-4827; 1090-2422; 1090-2422
• DOI: 10.1016/j.yexcr.2015.07.032

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. [Display omitted] •We evaluated the effect of HDL deficiency on skin morphology.•A mouse model lacking both apoA-I and apoE was generated.•Ultrastructural analysis revealed cholesterol deposition and foam cells in dermis.