Deficiency of the tetraspanin CD63 associated with kidney pathology but normal lysosomal function.
CD63 is a member of the tetraspanin superfamily that constitutes a main component of the lysosomal membrane. In mice, two CD63 gene loci are present, with only one of these two being functional. We generated and analyzed mice deficient for active CD63. Disruption of CD63 results in a complete loss of CD63 protein expression. Despite its abundance in late endosomes/lysosomes, the lack of CD63 does not cause obvious endosomal/lysosomal abnormalities. CD63 knockout mice are viable and fertile without gross morphological abnormalities in the majority of tissues. No alterations in the populations of immune cells and only minor differences in platelet function were observed. This suggests that the lack of CD63 could be successfully compensated for, most likely by other tetraspanins. However, CD63 deficiency leads to an altered water balance. CD63 knockout mice show an increased urinary flow, water intake, reduced urine osmolality, and a higher fecal water content. In principle cells of the collecting duct of CD63-deficient mice, abnormal intracellular lamellar inclusions were observed. This indicates that the sorting of apical transport proteins might be impaired in these cells. CD63 knockout mice provide an important tool for analyzing the various postulated functions of CD63 in vivo.
Schröder
Jenny
J
Biochemisches Institut, Christian-Albrechts Universität Kiel, Otto-Hahn-Platz 9, D-24118 Kiel, Germany.
Lüllmann-Rauch
Renate
R
Himmerkus
Nina
N
Pleines
Irina
I
Nieswandt
Bernhard
B
Orinska
Zane
Z
Koch-Nolte
Friedrich
F
Schröder
Bernd
B
Bleich
Markus
M
Saftig
Paul
P
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000235:genetics; D004231:Diuresis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018390:Gene Targeting; D016678:Genome / Q000235:genetics; D007107:Immune System / Q000166:cytology; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007685:Kidney Tubules, Collecting / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010979:Platelet Function Tests; D010980:Platelet Membrane Glycoproteins; D011544:Pseudogenes; D060149:Tetraspanin 30; D016482:Urinalysis; D014882:Water-Electrolyte Balance
D015703:Antigens, CD; C554587:Cd63 protein, mouse; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30