Characterization of the cheetah serum amyloid A1 gene: critical role and functional polymorphism of a cis-acting element.
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-kappaB) and CCAAT/enhancer binding protein beta (C/EBPbeta) 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-kappaB 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.
Zhang
Beiru
B
Department of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan.
Une
Yumi
Y
Ge
Fengxia
F
Fu
Xiaoying
X
Qian
Jinze
J
Zhang
Pengyao
P
Sawashita
Jinko
J
Higuchi
Keiichi
K
Mori
Masayuki
M
D002612:Acinonyx / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D000685:Serum Amyloid A Protein / Q000235:genetics* / Q000502:physiology*
D016328:NF-kappa B; D000685:Serum Amyloid A Protein