Multi-omic analyses in Abyssinian cats with primary renal amyloid deposits.

The amyloidoses constitute a group of diseases occurring in humans and animals that are characterized by abnormal deposits of aggregated proteins in organs, affecting their structure and function. In the Abyssinian cat breed, a familial form of renal amyloidosis has been described. In this study, multi-omics analyses were applied and integrated to explore some aspects of the unknown pathogenetic processes in cats. Whole-genome sequences of two affected Abyssinians and 195 controls of other breeds (part of the 99 Lives initiative) were screened to prioritize potential disease-associated variants. Proteome and miRNAome from formalin-fixed paraffin-embedded kidney specimens of fully necropsied Abyssinian cats, three affected and three non-amyloidosis-affected were characterized. While the trigger of the disorder remains unclear, overall, (i) 35,960 genomic variants were detected; (ii) 215 and 56 proteins were identified as exclusive or overexpressed in the affected and control kidneys, respectively; (iii) 60 miRNAs were differentially expressed, 20 of which are newly described. With omics data integration, the general conclusions are: (i) the familial amyloid renal form in Abyssinians is not a simple monogenic trait; (ii) amyloid deposition is not triggered by mutated amyloidogenic proteins but is a mix of proteins codified by wild-type genes; (iii) the form is biochemically classifiable as AA amyloidosis.

Complex segregation analysis of familial amyloidosis in Oriental shorthair cats.

Amyloidosis in Siamese/Oriental cats is a lethal condition with variable age of clinical onset. There is no sex predisposition and clinical signs of disease usually become apparent by 1-7 years of age. In the terminal stages, the liver is enlarged and pale, and contains parenchymal hemorrhages. In the present study, pedigree data from 17 cats with clinical signs consistent with amyloidosis underwent genetic analysis. Necropsy and histopathological data were available for 10 of the 17 cats. Necropsy findings included pale, fragile and enlarged livers with capsular ruptures and parenchymal hemorrhages, and sanguineous effusions in the abdominal cavity. Congo red staining with birefringence confirmed systemic amyloidosis mostly involving the liver and thyroid gland. In four of the 10 cases, protein deposits were classified as amyloid A protein (AA-amyloid) by immunostaining. Pedigree data for all 17 affected cats indicated a familial trait. Animal threshold model analysis demonstrated that the heritability for amyloidosis was 0.56 ± 0.09 (standard error). Complex segregation analysis was used for statistical comparisons among models to determine environmental or sex dependent effects, and Mendelian, polygenic, or mixed Mendelian and polygenic inheritance patterns. A mixed model with a Mendelian and polygenic component provided the best fit to the data and thus was most likely. All other models of inheritance were rejected due to their insufficient ability to explain segregation of amyloidosis. In conclusion, we found evidence for a complex genetic basis for amyloidosis in Oriental shorthair cats.

Changes in serum and urine SAA concentrations and qualitative and quantitative proteinuria in Abyssinian cats with familial amyloidosis: a five-year longitudinal study (2009-2014).

BACKGROUND: Diagnosis of familial amyloidosis (FA) in Abyssinian cats usually is made on postmortem examination. HYPOTHESIS/OBJECTIVES: Sequential analysis of serum SAA (sSAA), urinary SAA (uSAA), urinary protein:creatinine (UPC) ratio, or sodium-dodecylsulfate agarose gel electrophoresis (SDS-AGE) may facilitate early identification of cats with FA. ANIMALS: Twenty-three Abyssinian cats belonging to cattery A or B (low and high prevalence of FA, respectively). METHODS: Prospective longitudinal study using 109 blood and 100 urine samples collected over 4-year period every 4 months, if possible, or more frequently in case of illness. Cats that died during study were necropsied. Health status of live cats was checked 5 years after enrollment. Serum amyloid A (sSAA) and urinary SAA (uSAA) were measured using ELISA kit. The UPC ratio and SDS-AGE also was performed. RESULTS: Familial amyloidosis was not identified in cattery A, whereas 7/14 cats from cattery B had FA. Serum amyloid A concentrations were not significantly different between cats in catteries A and B or between cats with or without FA, despite frequent peaks in cats from cattery B. Conversely, uSAA was significantly higher in cattery B, especially in the terminal phases of FA. Proteinuria occasionally was found in cats from both catteries, especially in those with FA. Urine protein electrophoresis identified mixed proteinuria only in cats with FA. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum amyloid A and UPC ratio are not helpful for early identification of Abyssinian cats with FA. Conversely, increases in uSAA with or without mixed proteinuria may be found before onset of clinical signs in cats with FA.

Amyloidosis in the black-footed ferret (Mustela nigripes).

This study describes clinical, histologic, immunohistochemical and electron microscopic features of amyloid A amyloidosis occurring in black-footed ferrets (Mustela nigripes) from eight U.S. zoological institutions. Ferrets had nonregenerative anemia, serum chemistries consistent with chronic renal disease, and proteinuria. Amyloid was present in a variety of tissues, but it was most severe in renal glomeruli and associated with tubular protein loss and emaciation. Congo red/potassium permanganate (KMnO4) and immunohistochemical stains revealed that the amyloid was of the AA type. Concurrent diseases and genetic predisposition were considered the most important contributing factors to development of amyloidosis. Analysis of the genetic tree did not reveal convincing evidence of a common ancestor in the affected ferrets, but a genetic predisposition is likely because all the captive black-footed ferrets are related.