Identification and functional analysis of a naturally occurring E89K mutation in the ABCA1 gene of the WHAM chicken

Alan D. Attie, Yannick Hamon, Angela R. Brooks-Wilson, Mark P. Gray-Keller, Marcia L. E. MacDonald, Veronique Rigot, Angie Tebon, Lin-Hua Zhang, Jacob D. Mulligan, Roshni R. Singaraja, J. James Bitgood, Mark E. Cook, John J. P. Kastelein, Giovanna Chimini, Michael R. Hayden

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Scopus)

Abstract

The Wisconsin hypoalpha mutant (WHAM) chicken has a >90% reduction in plasma HDL due to hypercatabolism. by the kidney of lipid-poor apoA-I. The WHAM chickens have a recessive white skin phenotype caused by a single-gene mutation that maps to the chicken Z-chromosome. This corresponds to human 9q31.1, a chromosomal segment that contains the ATP-binding cassette protein-1 (ABCA1) gene, which is mutated in Tangier Disease and familial hypoalphalipoproteinemia. Complete sequencing of the WHAM ABCA1 cDNA identified a missense mutation near the N-terminus of the protein (E89K). The substitution of this evolutionary conserved glutamate residue for lysine in the mouse ABCA1 transporter leads to complete loss of function, resulting principally from defective intracellular trafficking and very little ABCA1 reaching the plasma membrane. The WHAM chicken is a naturally occurring animal model for Tangier Disease.-Attie, A. D., Y. Hamon, A. R. Brooks-Wilson, M. P. Gray-Keller, M. L. E. MacDonald, V. Rigot, A. Tebon, L.-H. Zhang, J. D. Mulligan, R. R. Singaraja J.J. Bitgood, M. E. Cook, J.J. P. Kastelein, G. Chimini, and M. R. Hayden. Identification and functional analysis of a naturally occurring E89K mutation in the ABCA1 gene of the WHAM chicken
Original languageEnglish
Pages (from-to)1610-1617
JournalJournal of Lipid Research
Volume43
Issue number10
DOIs
Publication statusPublished - 2002

Cite this