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Increased expression of lysosomal acid phosphatase in CLN3‐defective cells and mouse brain tissue
Author(s) -
Pohl Sandra,
Mitchison Hannah M.,
Kohlschütter Alfried,
Diggelen Otto van,
Braulke Thomas,
Storch Stephan
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04920.x
Subject(s) - batten disease , lysosomal storage disease , lysosome , biology , lipofuscin , acid phosphatase , neuronal ceroid lipofuscinosis , microbiology and biotechnology , gene knockdown , cerebellum , endocrinology , medicine , biochemistry , enzyme , gene
Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative disorder caused by defective function of the lysosomal membrane glycoprotein CLN3. The activity of the lysosomal acid phosphatase (LAP/ACP2) was found to be significantly increased in the cerebellum and brain stem of Cln3‐ targeted mice during the early stages of postnatal life. Histochemical localization studies revealed an increased LAP/ACP2 staining intensity in neurons of the cerebral cortex of 48‐week‐old Cln3‐ targeted mice as compared with controls. Additionally, the expression of another lysosomal membrane protein LAMP‐2 was increased in all brain areas. Knockdown of CLN3 expression in HeLa cells by RNA interference also resulted in increased LAP/ACP2 and LAMP‐2 expression. Finally in fibroblasts of two juvenile neuronal ceroid lipofuscinosis patients elevated levels of LAP/ACP2 were found. Both activation of gene transcription and increased protein half‐life appear to contribute to increased LAP/ACP2 protein expression in CLN3‐deficient cells. The data suggest that lysosomal dysfunction and accumulation of storage material require increased biogenesis of LAP/ACP2 and LAMP‐2 positive membranes which makes LAP/ACP2 suitable as biomarker of Batten disease.