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Deficiency of the tetraspanin CD63 associated with kidney pathology but normal lysosomal function

Jenny Schröder1, Renate Lüllmann-Rauch, Nina Himmerkus

  • 1Biochemisches Institut, Christian-Albrechts Universität Kiel, Otto-Hahn-Platz 9, D-24118 Kiel, Germany.

Molecular and Cellular Biology
|December 17, 2008
PubMed

Insights

Mice lacking the CD63 protein, a lysosomal membrane component, show normal development but altered water balance. This CD63 knockout model reveals potential roles in kidney function and protein transport.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • CD63 is a tetraspanin protein crucial for lysosomal function.
  • Mice possess two CD63 gene loci, with only one being functional.

Purpose of the Study:

  • To investigate the in vivo functions of CD63 by generating and analyzing CD63-deficient mice.
  • To assess the physiological consequences of complete CD63 loss.

Main Methods:

  • Generation of CD63 knockout mice.
  • Analysis of protein expression, tissue morphology, immune cell populations, platelet function, and water balance.
  • Histological examination of kidney collecting duct cells.

Main Results:

  • CD63 knockout mice exhibit normal viability, fertility, and general morphology, with no significant immune cell alterations.
  • Despite CD63's lysosomal localization, no major endosomal/lysosomal abnormalities were observed.
  • CD63 deficiency resulted in impaired water balance, characterized by increased urinary flow, water intake, reduced urine osmolality, and higher fecal water content.
  • Abnormal intracellular lamellar inclusions and potential apical protein sorting defects were noted in kidney collecting duct cells.

Conclusions:

  • The absence of CD63 can be compensated by other tetraspanins in most tissues, leading to normal development and physiology.
  • CD63 plays a significant role in regulating water balance and potentially apical protein transport in the kidney collecting duct.
  • CD63 knockout mice serve as a valuable tool for further research into CD63's diverse biological functions.

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