Apolipoprotein C-III amyloidosis in white lions ( Panthera leo )

• Published in: Veterinary pathology p. 3009858241230100
• Main Authors: Kobayashi, Natsumi, Iwaide, Susumu, Fukui, Hiroto, Une, Yumi, Itoh, Yoshiyuki, Hisada, Miki, Murakami, Tomoaki
• Format: Journal Article
• Language: English
• Published: United States 01.07.2024
• Subjects: aging disease; mass spectrometry; Panthera leo; amyloid; apolipoprotein C-III
• ISSN: 1544-2217
• DOI: 10.1177/03009858241230100

Apolipoprotein C-III (ApoC-III) amyloidosis in humans is a hereditary amyloidosis caused by a D25V mutation in the gene. This condition has only been reported in a French family and not in animals. We analyzed a 19-year-old white lion ( ) that died in a Japanese safari park and found renal amyloidosis characterized by severe deposition confined to the renal corticomedullary border zone. Mass spectrometry-based proteomic analysis identified ApoC-III as a major component of renal amyloid deposits. Amyloid deposits were also positive for ApoC-III by immunohistochemistry. Based on these results, this case was diagnosed as ApoC-III amyloidosis for the first time in nonhuman animals. Five additional white lions were also tested for amyloid deposition retrospectively. ApoC-III amyloid deposition was detected in 3 white lions aged 19 to 21 years but not in 2 cases aged 0.5 and 10 years. Genetic analysis of white and regular-colored lions revealed that the sequences of the lions were identical, regardless of amyloid deposition. These results suggest that ApoC-III amyloidosis in lions, unlike in humans, may not be a hereditary condition but an age-related condition. Interestingly, lion ApoC-III has a Val30 substitution compared with other species of that have Met30. Structural predictions suggest that the conformation of ApoC-III with Met30 and ApoC-III with Val30 are almost identical, but this substitution may alter the ability to bind to lipids. As with the D25V mutation in human ApoC-III, the Val30 substitution in lions may increase the proportion of free ApoC-III, leading to amyloid formation.