Tokyo University of Agriculture and Technology, Tokyo, Japan.
Swine and Poultry Research Center, Shizuoka, Japan.
Toxicol Pathol. 2023 Jul;51(5):257-263. doi: 10.1177/01926233231204019. Epub 2023 Oct 24.
The minipig has been used as a non-rodent species in nonclinical toxicology studies, but little is known about amyloid A (AA) amyloidosis in this species. Among domestic pigs, reports of AA amyloidosis have been limited to animals with mutations in the N-terminal residue of serum AA (SAA), which is thought to be a primary etiological factor. In this study, we histologically examined 26 microminipigs aged 0.6 to 10 years and observed amyloid deposition in one 0.6-year-old and six 5-year-old or older microminipigs. The amyloid deposits were identified as AA based on mass spectrometry (MS) and immunohistochemistry (IHC). The 0.6-year-old microminipig showed severe deposition in the renal cortex and spleen, whereas 5-year-old or older animals had severe deposition in the renal medulla. MS and IHC detected serum amyloid P-component (SAP) in amyloid deposits in older animals but not in a 0.6-year-old animals. Based on the proteomic analysis and gene sequencing, amino acid mutations of SAA, previously found in domestic pigs, were not involved in the pathogenesis of AA amyloidosis in microminipigs. This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.
小型猪已被用作非啮齿类动物在非临床毒理学研究中，但对该物种的淀粉样 A (AA) 淀粉样变性知之甚少。在家猪中，AA 淀粉样变性的报道仅限于血清 AA（SAA）N 末端残基发生突变的动物，这被认为是主要的病因。在这项研究中，我们对 26 头年龄为 0.6 至 10 岁的微型猪进行了组织学检查，在 1 头 0.6 岁和 6 头 5 岁或以上的微型猪中观察到淀粉样物质沉积。根据质谱（MS）和免疫组织化学（IHC），淀粉样沉积物被鉴定为 AA。0.6 岁的微型猪的肾脏皮质和脾脏有严重的沉积，而 5 岁或以上的动物则有严重的肾髓质沉积。MS 和 IHC 在老年动物的淀粉样沉积物中检测到血清淀粉样蛋白 P 成分（SAP），但在 0.6 岁的动物中未检测到。基于蛋白质组分析和基因测序，在小型猪中发现的 SAA 氨基酸突变与野生型 SAA 参与 AA 淀粉样变性的发病机制无关。这项研究表明，野生型 SAA 的微型猪会发生 AA 淀粉样变性，并提出了淀粉样周围环境（如 SAP）的差异可能影响病理表型差异的可能性。
