Spontaneous high density lipoprotein deficiency syndrome associated with a Z-linked mutation in chickens.

A mutant strain of chicken previously identified by a "recessive white skin" phenotype was found to have a profound deficiency in high density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). ApoA-I levels in the mutant chickens were reduced by greater than 90%. Since HDL is the predominant cholesterol transporter in chickens, the HDL deficiency was associated with a greater than 80% decrease in total plasma cholesterol. The mutation segregates with markers linked to the Z-chromosome. The structure of the apoA-I produced by the mutant chickens appeared normal as judged by two-dimensional gel electrophoresis. The genetic and biochemical evidence, therefore, suggests that the mutation is not in the apoA-I structural gene. Turnover studies were performed on labeled HDL or on labeled apoA-I preincubated with HDL prior to intravenous injection. Both types of experiments showed that both defective apoA-I production and hypercatabolism contributed to the HDL deficiency, although defective production made a much larger contribution.