Normal Lysosomal Morphology and Function in LAMP-1-deficient Mice*
- Nicole Andrejewski‡,
- Eeva-Liisa Punnonen§,
- Gundula Guhde‡,
- Yoshitaka Tanaka‡¶,
- Renate Lüllmann-Rauch‖,
- Dieter Hartmann‖,
- Kurt von Figura‡ and
- Paul Saftig‡**
- From ‡Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universität Göttingen, 37073 Göttingen, Germany, the §Institute of Biotechnology and Electron Microscopy, University of Helsinki, FIN-00014 Helsinki, Finland, and ‖Anatomisches Institut der Universität Kiel, Otto-Hahn-Platz 8, 24043 Kiel, Germany
Abstract
Lysosomal membranes contain two highly glycosylated proteins, designated LAMP-1 and LAMP-2, as major components. LAMP-1 and LAMP-2 are structurally related. To investigate the physiological role of LAMP-1, we have generated mice deficient for this protein. LAMP-1-deficient mice are viable and fertile. In LAMP-1-deficient brain, a mild regional astrogliosis and altered immunoreactivity against cathepsin-D was observed. Histological and ultrastructural analyses of all other tissues did not reveal abnormalities. Lysosomal properties, such as enzyme activities, lysosomal pH, osmotic stability, density, shape, and subcellular distribution were not changed in comparison with controls. Western blot analyses of LAMP-1-deficient and heterozygote tissues revealed an up-regulation of the LAMP-2 protein pointing to a compensatory effect of LAMP-2 in response to the LAMP-1 deficiency. The increase of LAMP-2 was neither correlated with an increase in the level oflamp-2 mRNAs nor with increased half-life time of LAMP-2. This findings suggest a translational regulation of LAMP-2 expression.
Footnotes
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↵* This work was supported in part by Deutsche Forschungsgemeinschaft Grant Sa 683/1–1.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ Supported in part by the Mochida Memorial Foundation for Medical and Pharmaceutical Research and the Yamanouchi Foundation for Research on Metabolic Disorders.
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↵** To whom correspondence and reprint requests should be addressed: Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universität Göttingen, Goßlerstraße 12D, 37073 Göttingen, Germany. Tel.: 49-551-395932; Fax: 49-551-395979; E-mail: saftig{at}uni-bc2.gwdg.de.
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↵2 P. Saftig, unpublished data.
- Abbreviations:
- bp
-
base pair(s)
- kbp
-
kilobase pair(s)
- kb
-
kilobase(s)
- PCR
-
polymerase chain reaction
- PBS
-
phosphate-buffered saline
- BSA
-
bovine serum albumin
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- Received August 11, 1998.
- Revision received January 20, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
