Abcd1-flox Mouse

Abcd1, encoding a peroxisomal ABC half-transporter (ALDP), is crucial for the import of very long-chain fatty acids (VLCFA) into the peroxisome. Mutations in Abcd1 lead to X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disorder. ABCD1-related pathways involve peroxisomal β-oxidation of VLCFA, and its normal function is vital for maintaining cellular lipid homeostasis [1,3,4,5,6,7].

In Abcd1-deficient mice, lipidome analyses revealed increased levels of cholesterol esters (CE) containing VLCFA. Under high-cholesterol loading, gene expression changes related to cholesterol metabolism were observed in human X-ALD fibroblasts. These included increased SOAT1 (converting cholesterol to CE) and lipid droplet formation, as well as upregulated NCEH1 (catalyzing CE hydrolysis), ABCA1 (cholesterol transporter), and cholesterol efflux. Similar changes were confirmed in the spinal cord of X-ALD mice, where Apoe (CNS cholesterol transporter) expression was also elevated [2].

In conclusion, Abcd1 is essential for VLCFA import into peroxisomes, maintaining lipid homeostasis. Studies on Abcd1-deficient mouse models have revealed its role in cholesterol metabolism in the context of X-ALD, providing insights into the pathophysiology of this disorder.