Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons

Masato Koike, Hiroshi Nakanishi, Paul Saftig, Junji Ezaki, Kyoko Isahara, Yoshiyuki Ohsawa, Walter Schulz-Schaeffer, Tsuyoshi Watanabe, Satoshi Waguri, Satoshi Kametaka, Masahiro Shibata, Kenji Yamamoto, Eiki Kominami, Christoph Peters, Kurt Von Figura, Yasuo Uchiyama

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Abstract

Cathepsin D-deficient (CD-/-) mice have been shown to manifest seizures and become blind near the terminal stage [approximately postnatal day (P) 26]. We therefore examined the morphological, immunocytochemical, and biochemical features of CNS tissues of these mice. By electron microscopy, autophagosome/autolysosome-like bodies containing part of the cytoplasm, granular osmiophilic deposits, and fingerprint profiles were demonstrated in the neuronal perikarya of CD-/-mouse brains after P20. Autophagosomes and granular osmiophilic deposits were detected in neurons at PO but were few in number, whereas they increased in the neuronal perikarya within days after birth. Some large-sized neurons having autophagosome/autolysosome-like bodies in the perikarya appeared in the CNS tissues, especially in the thalamic region and the cerebral cortex, at P17. These lysosomal bodies occupied the perikarya of almost all neurons in CD-/- mouse brains obtained from P23 until the terminal stage. Because these neurons exhibited autofluorescence, it was considered that ceroid lipofuscin may accumulate in lysosomal structures of CD-/- neurons. Subunit c of mitochondrial ATP synthase was found to accumulate in the lysosomes of neurons, although the activity of tripeptidyl peptidase-significantly increased in the brain. Moreover, neurons near the terminal stage were often shrunken and possessed irregular nuclei through which small dense chromatin masses were scattered. These results suggest that the CNS neurons in CD-/- mice show a new form of lysosomal accumulation disease with a phenotype resembling neuronal ceroid lipofuscinosis.

Original languageEnglish
Pages (from-to)6898-6906
Number of pages9
JournalJournal of Neuroscience
Volume20
Issue number18
Publication statusPublished - Sep 15 2000

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Ceroid
Lipofuscin
Cathepsin D
Neurons
Brain
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Mitochondrial Proton-Translocating ATPases
Neuronal Ceroid-Lipofuscinoses
Dermatoglyphics
Lysosomes
Human Body
Cerebral Cortex
Chromatin
Electron Microscopy
Cytoplasm
Seizures
Parturition
Phenotype

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Koike, M., Nakanishi, H., Saftig, P., Ezaki, J., Isahara, K., Ohsawa, Y., ... Uchiyama, Y. (2000). Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. Journal of Neuroscience, 20(18), 6898-6906.

Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. / Koike, Masato; Nakanishi, Hiroshi; Saftig, Paul; Ezaki, Junji; Isahara, Kyoko; Ohsawa, Yoshiyuki; Schulz-Schaeffer, Walter; Watanabe, Tsuyoshi; Waguri, Satoshi; Kametaka, Satoshi; Shibata, Masahiro; Yamamoto, Kenji; Kominami, Eiki; Peters, Christoph; Von Figura, Kurt; Uchiyama, Yasuo.

In: Journal of Neuroscience, Vol. 20, No. 18, 15.09.2000, p. 6898-6906.

Research output: Contribution to journalArticle

Koike, M, Nakanishi, H, Saftig, P, Ezaki, J, Isahara, K, Ohsawa, Y, Schulz-Schaeffer, W, Watanabe, T, Waguri, S, Kametaka, S, Shibata, M, Yamamoto, K, Kominami, E, Peters, C, Von Figura, K & Uchiyama, Y 2000, 'Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons', Journal of Neuroscience, vol. 20, no. 18, pp. 6898-6906.
Koike M, Nakanishi H, Saftig P, Ezaki J, Isahara K, Ohsawa Y et al. Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. Journal of Neuroscience. 2000 Sep 15;20(18):6898-6906.
Koike, Masato ; Nakanishi, Hiroshi ; Saftig, Paul ; Ezaki, Junji ; Isahara, Kyoko ; Ohsawa, Yoshiyuki ; Schulz-Schaeffer, Walter ; Watanabe, Tsuyoshi ; Waguri, Satoshi ; Kametaka, Satoshi ; Shibata, Masahiro ; Yamamoto, Kenji ; Kominami, Eiki ; Peters, Christoph ; Von Figura, Kurt ; Uchiyama, Yasuo. / Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 18. pp. 6898-6906.
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AU - Isahara, Kyoko

AU - Ohsawa, Yoshiyuki

AU - Schulz-Schaeffer, Walter

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AU - Kametaka, Satoshi

AU - Shibata, Masahiro

AU - Yamamoto, Kenji

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AU - Von Figura, Kurt

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