Title
Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1
Author
Jong, M.C.
Gijbels, M.J.J.
Dahlmans, V.E.H.
van Gorp, P.J.J.
Koopman, S.-J.
Ponec, M.
Hofker, M.H.
Havekes, L.M.
Gaubius instituut TNO
Publication year
1998
Abstract
Transgenic mice were generated with different levels of human apolipoprotein C1 (APOC1) expression in liver and skin. At 2 mo of age, serum levels of cholesterol, triglycerides (TG), and FFA were strongly elevated in APOC1 transgenic mice compared with wild-type mice. These elevated levels of serum cholesterol and TG were due mainly to an accumulation of VLDL particles in the circulation. In addition to hyperlipidemia, APOC1 transgenic mice developed dry and scaly skin with loss of hair, dependent on the amount of APOC1 expression in the skin. Since these skin abnormalities appeared in two independent founder lines, a mutation related to the specific insertion site of the human APOC1 gene as the cause for the phenotype can be excluded. Histopathological analysis of high expressor APOC1 transgenic mice revealed a disorder of the skin consisting of epidermal hyperplasia and hyperkeratosis, and atrophic sebaceous glands lacking sebum. In line with these results, epidermal lipid analysis showed that the relative amounts of the sebum components TG and wax diesters in the epidermis of high expressor APOC1 transgenic mice were reduced by 60 and 45%, respectively. In addition to atrophic sebaceous glands, the melbomian glands were also found to be severely atrophic in APOC1 transgenic mice. High expressor APOC1 transgenic mice also exhibited diminished abdominal adipose tissue stores (a 60% decrease compared with wild-type mice) and a complete deficiency of subcutaneous fat. These results indicate that, in addition to the previously reported inhibitory role of apoC1 on hepatic remnant uptake, overexpression of apoC1 affects lipid synthesis in the sebaceous gland and/or epidermis as well as adipose tissue formation. These APOC1 transgenic mice may serve as an interesting in vivo model for the investigation of lipid homeostasis in the skin.
Subject
Health
Apolipoprotein C
Hypertriglyceridemia
Sebaceous glands
Sebum production
Triglycerides
Animals
Apolipoprotein C-I
Apolipoproteins C
Epidermis
Female
Humans
Hyperlipidemias
Lipids
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Skin Abnormalities
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DOI
https://doi.org/10.1172/jci791
TNO identifier
234283
ISSN
0021-9738
Source
Journal of Clinical Investigation, 101 (1), 145-152
Document type
article