Relationship between genetic polymorphism and renal amyloidosis, a serious disease in cats, discovered!
Relationship between genetic polymorphism and renal amyloidosis, a serious disease in cats, discovered!
A research team led by Associate Professor Tomoaki Murakami of Tokyo University of Agriculture and Technology Graduate School Institute of Agriculture Division of Animal Life Science of the National University Corporation has pathologically analyzed five mongrel cats who died of systemic AA amyloidosis and found that the distribution of amyloid deposits in the kidneys is correlated with genetic polymorphisms in the serum amyloid A (SAA) protein, which is the material for amyloid. This is the first time that differences in the sequence of causative proteins (polymorphisms) have been proven to lead to differences in the distribution of amyloid in organs. Since differences in the distribution of amyloid deposits in organs are strongly related to clinical symptoms, the results of this study are expected to be applied to the prediction of amyloid deposition distribution by genetic analysis and the selection of treatment targets.
The results of this research were published in Scientific Reports on July 1st.
Paper title: Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats
URL: https://doi.org/10.1038/s41598-025-07983-7
current situation
Amyloidosis is a group of diseases in which proteins derived from the body are abnormally folded, forming fibrous substances called "amyloids," which are deposited in various tissues and cause functional disorders. They are classified according to the difference in the causative protein, and AA amyloidosis is caused by the abnormal aggregation and deposition of serum amyloid A (SAA) protein, which is produced in association with inflammation, and is one of the most common forms of amyloidosis in animals and humans.
In feline AA amyloidosis, amyloid deposits widely in organs such as the liver, spleen, and kidneys, causing organ damage. Amyloid deposits progressively in association with inflammatory diseases such as stomatitis, leading to death from liver or kidney failure, but there is currently no established treatment, and the disease is considered intractable. It is known that amyloid deposits in different areas of the kidney, such as the glomerulus, peritubular area, and renal papilla, causing symptoms according to the area of deposition, but the factors that cause differences in the area of deposition have not been clarified until now.
Research Structure
This study was conducted by Dr. Natsumi Kobayashi of Graduate School of Agriculture Cooperative Division of Veterinary Sciences Tokyo University of Agriculture and Technology Graduate School, Associate Professor. Masahiro Kaneda of the Graduate Institute of Agriculture Division of Animal Life Science School of Veterinary Medicine, of the Graduate School of Veterinary Medicine, Japan University, Dr. Mitsuhiro Ikeda and Dr. Hiro Associate Professor Hirotaka Kondo of the Department of Veterinary Medicine, University Graduate School of Veterinary Medicine, Dr. Susumu Iwaide of Tokyo University of Agriculture and Technology Graduate School Graduate School of Agriculture Cooperative Division of Veterinary Sciences, Tokyo University of Agriculture and Technology Smart-Core-Facility Promotion Organization Yoshiyuki Itoh Associate Professor and Dr. Miki Hisada, Tokyo University of Agriculture and Technology Faculty of Agriculture Cooperative Department of Veterinary Medicine Yuka Kato (alumni), Dr. Niki Sedghi Masoud (Graduate Graduate School of Agriculture Cooperative Division of Veterinary Sciences of the same university), Dr. Kohji Nomura of the Department of Pathology of MLT Co., Ltd., It was conducted by Dr. Machie Tsuneyasu and Ms. Tomoko Akamine of Watanabe Animal Hospital (Anicom Group) and Associate Professor Tomoaki Murakami of Tokyo University of Agriculture and Technology Graduate School Institute of Agriculture Division of Animal Life Science. This research was supported by JSPS Grants-in-Aid for Scientific Research (23H02380) and JST Industry-Academia Co-Creation Platform Joint Research Promotion Program (OPERA).
Research results
The research team first conducted histopathological analysis of the kidneys of five cross-breed cats that had died in Japan. The results showed that amyloid deposits were found in the glomeruli and renal papillae of all cats, but there were significant individual differences in the deposition patterns in the medulla. To clarify what factors caused these differences in deposition in the medulla, the research team focused on the gene sequence of SAA, an amyloid precursor protein.
Analysis of the SAA gene of each individual revealed multiple gene polymorphisms with differences in amino acid sequence at six locations. The research team focused on whether the 45th amino acid in the SAA protein is glutamine (SAA Q45) or arginine (SAA R45) among these SAA polymorphisms, and performed immunohistochemical analysis using antibodies that specifically recognize SAA Q45 or SAA R45, as well as mass spectrometry of amyloid deposits recovered from each area of the kidney. The results showed that amyloid derived from SAA Q45 was deposited mainly in the glomeruli and papilla of the renal cortex, while amyloid derived from SAA R45 was deposited in the tubular basement membrane of the medulla (Figure 1).
Cats inherit several SAA genes from both parents. Interestingly, in individuals expressing both SAA Q45 and SAA R45, the respective amyloids were deposited separately. This finding is extremely important in understanding the pathology of amyloidosis, as it shows that differences in the primary structure (amino acid sequence) of the causative protein determine the location of the lesions.
Amyloid derived from SAA with glutamine at position 45 (AA with Q45) is deposited in the glomeruli and papilla of the kidney (left route), whereas amyloid derived from SAA with arginine at position 45 (AA with R45) is deposited in the medulla and papilla of the kidney (right route).
Future challenges
In cats with AA amyloidosis, the degree of deposition varies throughout the organs, but it is still unclear how the distribution pattern affects clinical symptoms. Since each structure of the kidney, such as the glomerulus, medulla, and papilla, has a different function, it is thought that symptoms and disease progression will vary greatly depending on which part is damaged. If technology is established in the future to predict and evaluate the site of amyloid deposition before death, it is expected that this will lead to improved accuracy in diagnosis of AA amyloidosis, an intractable disease in cats, and the realization of personalized preventive medicine.
◆Inquiries about research◆
Tokyo University of Agriculture and Technology Graduate School Institute of Agriculture
Division of Animal Life Science Associate Professor
Tomoaki Murakami
TEL：042－367－5883
E-mail: mrkmt (please insert @ here)cc.tuat.ac.jp
URL：http://web.tuat.ac.jp/~tatlvt/
Press Release (PDF:504.8KB)
Related links (opens in new window)
- Tokyo University of Agriculture and Technology Tomoaki Murakami Associate Professor Researcher Profile
- Tokyo University of Agriculture and Technology Masahiro Kaneda Associate Professor Researcher Profile
- Tokyo University of Agriculture and Technology Yoshiyuki Itoh Associate Professor Researcher Profile
- Tokyo University of Agriculture and Technology Tomoaki Murakami Associate Professor Laboratory Website
- Tomoaki Murakami Associate Professor and Masahiro Kaneda Associate Professor belong to Tokyo University of Agriculture and Technology Faculty of Agriculture Cooperative Department of Veterinary Medicine