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Carnitine palmitoyltransferase‐1c gain‐of‐function in the brain results in postnatal microencephaly
Author(s) -
Reamy Amanda A.,
Wolfgang Michael J.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07312.x
Subject(s) - medicine , endocrinology , carnitine , biology , genetically modified mouse , weaning , transgene , malonyl coa , weight gain , body weight , beta oxidation , metabolism , gene , biochemistry
J. Neurochem. (2011) 118 , 388–398. Abstract Carnitine palmitoyltransferase‐1c (CPT1c) is a newly identified and poorly understood brain‐specific CPT1 homologue. Here, we have generated a new animal model that allows the conditional expression of CPT1c in a tissue specific and/or temporal manner via Cre‐lox mediated recombination. Brain‐specific, exogenous expression of CPT1c was achieved by crossing transgenic CPT1c mice to Nestin‐Cre mice. The resulting double transgenic mice (CPT1c‐TgN) displayed severe growth retardation in the postnatal period with a stunted development at 2 weeks of age. CPT1c‐TgN mice had a greater than 2.3‐fold reduction in brain weight. Even with this degree of microencephaly, CPT1c‐TgN mice were viable and fertile and exhibited normal post‐weaning growth. When fed a high fat diet CPT1c‐TgN mice were protected from weight gain and the difference in body weight between CPT1c‐TgN and control mice was further exaggerated. Conversely, low fat, high carbohydrate feeding partially reversed the body weight defects in CPT1c‐TgN mice. Analysis of total brain lipids of low fat fed mice revealed a depletion of total very long chain fatty acids in adult CPT1c‐TgN mice which was not evident in high fat fed CPT1c‐TgN mice. These data show that CPT1c can elicit profound effects on brain physiology and total fatty acid profiles, which can be modulated by the nutritional composition of the diet.