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Journal of Heredity Advance Access published online on March 28, 2008
Journal of Heredity, doi:10.1093/jhered/esn015
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© The American Genetic Association. 2008. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Characterization of the Cheetah Serum Amyloid A1 Gene: Critical Role and Functional Polymorphism of a Cis-Acting Element

Beiru Zhang, Yumi Une, Fengxia Ge, Xiaoying Fu, Jinze Qian, Pengyao Zhang, Jinko Sawashita, Keiichi Higuchi, and Masayuki Mori

From the Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan (Zhang, Ge, Fu, Qian, Zhang, Sawashita, Higuchi, and Mori); the Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University 1-17-71 Fuchinobe, Sagamihara, Kanagawa, 229-8501, Japan (Une); and the Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China (Zhang)

Address correspondence to M. Mori at the address above, or e-mail: masamori{at}sch.md.shinshu-u.ac.jp.

Amyloid A (AA) amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction. For practical conservation of this species, therefore, it is critical to elucidate the etiology of AA amyloidosis, especially to understand the mechanisms of transcriptional regulation of serum amyloid A (SAA), a precursor protein of the AA protein. In this study, the structure and nucleotide sequence of the cheetah SAA1 gene including the 5'-flanking promoter/enhancer region was determined. Putative nuclear factor kappa-B (NF-{kappa}B) and CCAAT/enhancer binding protein β (C/EBPβ) cis-acting elements, which play key roles in SAA1 transcriptional induction in response to inflammation, were identified in the 5'-flanking region of the cheetah SAA1 gene. Fortuitously, a single nucleotide polymorphism was identified in the captive cheetah cohort in the putative NF-{kappa}B cis-acting element and had a remarkable effect on SAA1 transcriptional induction. These results provide a foundation not only for clarifying the etiology of AA amyloidosis in the cheetah but also for contriving a strategy for conservation of this species.

Corresponding Editor: William Modi

Received October 19, 2007
Accepted January 16, 2008


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