Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Cell Tissue Res. 2011 Nov;346(2):141-9. doi: 10.1007/s00441-011-1252-0. Epub 2011 Oct 14.
Tripeptidyl peptidase I (TPPI) - a lysosomal serine protease - is encoded by the CLN2 gene, mutations that cause late-infantile neuronal ceroid lipofuscinosis (LINCL) connected with profound neuronal loss, severe clinical symptoms and early death at puberty. Developmental studies of TPPI activity levels and distribution have been done in the human and rat central nervous systems (CNS) and visceral organs. Similar studies have not been performed in mouse. In this paper, we follow up on the developmental changes in the enzyme activity and localization pattern in the CNS and visceral organs of mouse over the main periods of life - embryonic, neonate, suckling, infantile, juvenile, adult and aged - using biochemical assays and enzyme histochemistry. In the studied peripheral organs (liver, kidney, spleen, pancreas and lung) TPPI is present at birth but further its pattern is not consistent in different organs over different life periods. TPPI activity starts to be expressed in the brain at the 10th embryonic day but in most neuronal types it appears at the early infantile period, increases during infancy, reaches high activity levels in the juvenile period and is highest in adult and aged animals. Thus, in mice TPPI activity becomes crucial for the neuronal functions later in development (juvenile period) than in humans and does not decrease with aging. These results are essential as a basis for comparison between normal and pathological TPPI patterns in mice. They can be valuable in view of the use of animal models for studying LINCL and other neurodegenerative disorders.
三肽基肽酶 I（TPPI）-一种溶酶体丝氨酸蛋白酶-由 CLN2 基因编码，该基因的突变导致晚发性婴儿神经元蜡样脂褐质沉积症（LINCL），与严重的神经元丧失、严重的临床症状和青春期早期死亡有关。在人和大鼠中枢神经系统（CNS）和内脏器官中已经进行了 TPPI 活性水平和分布的发育研究。在小鼠中尚未进行类似的研究。在本文中，我们通过生化分析和酶组织化学研究，在胚胎、新生、哺乳、婴儿、幼年、成年和老年等主要生命阶段，研究了 CNS 和内脏器官中酶活性和定位模式的发育变化。在所研究的外周器官（肝、肾、脾、胰腺和肺）中，TPPI 在出生时存在，但在不同生命阶段不同器官中的模式不一致。TPPI 活性在第 10 天的胚胎期开始在大脑中表达，但在大多数神经元类型中，它在婴儿早期出现，在婴儿期增加，在青少年期达到高活性水平，在成年和老年动物中最高。因此，在小鼠中，TPPI 活性对于发育后期（青少年期）的神经元功能变得至关重要，而不像人类那样随着年龄的增长而降低。这些结果是比较小鼠正常和病理 TPPI 模式的基础，对于研究 LINCL 和其他神经退行性疾病的动物模型具有重要价值。
