Abstract
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.
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Fig. S1
Grading of TPPI activity levels on the example of Purkinje cells. Low enzyme activity at 22 PD is graded with one plus (+) (a). Substantial TPPI activity at 33 PD graded with two pluses (++) (b). High enzyme activity at 49 PD – (+++) (c). Bars 25 μm (JPEG 311 kb)
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Dimitrova, M., Deleva, D., Pavlova, V. et al. Developmental study of tripeptidyl peptidase I activity in the mouse central nervous system and peripheral organs. Cell Tissue Res 346, 141–149 (2011). https://doi.org/10.1007/s00441-011-1252-0
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DOI: https://doi.org/10.1007/s00441-011-1252-0