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LIMP-2/LGP85 deficiency causes ureteric pelvic junction obstruction, deafness and peripheral neuropathy in mice.

In previous overexpression studies we revealed a role for the lysosomal membrane protein LIMP-2/LGP85 in lysosomal biogenesis. LIMP-2-deficient mice show an increased postnatal mortality which is associated with a development of a uni- or bilateral hydronephrosis caused by an obstruction of the ureteropelvic junction. An accumulation of lysosomes in epithelial cells of the ureter adjacent to the ureteral lumen and a disturbed apical expression of uroplakin was observed, suggesting an impairment of membrane transport processes. Serious hearing impairment in LIMP-2-deficient animals was indicated by deficits in acoustic startle responses, in brainstem evoked auditory potentials and a reduced endochondral potential. LIMP-2-deficient mice suffer from a massive decline of spiral ganglia in the cochlea concomitant with that of the inner and outer hair cells. These pathological changes begin at the age of 3 months and are probably secondary to a degeneration of the stria vascularis. LIMP-2-deficient mice are also characterized by a peripheral demyelinating neuropathy. Demyelinization was found to be associated with a massive loss of peripheral myelin proteins and an increased activity and expression of lysosomal proteins highlighting a hitherto unknown role of the lysosomal compartment in the development of this myelination disorder. The phenotype of LIMP-2-deficient mice stimulates the search for mutations in human disorders associated with degeneration of the stria vascularis and/or demyelinization of peripheral nerves.

Pubmed ID: 12620969


  • Gamp AC
  • Tanaka Y
  • L├╝llmann-Rauch R
  • Wittke D
  • D'Hooge R
  • De Deyn PP
  • Moser T
  • Maier H
  • Hartmann D
  • Reiss K
  • Illert AL
  • von Figura K
  • Saftig P


Human molecular genetics

Publication Data

March 15, 2003

Associated Grants


Mesh Terms

  • Animals
  • Animals, Newborn
  • Antigens, CD36
  • Biological Transport
  • Blotting, Southern
  • Blotting, Western
  • Cathepsin D
  • Cell Membrane
  • Cochlea
  • Deafness
  • Demyelinating Diseases
  • Epithelial Cells
  • Evoked Potentials, Auditory
  • Exons
  • Fibroblasts
  • Genotype
  • Hypertrophy
  • Kidney
  • Lysosome-Associated Membrane Glycoproteins
  • Lysosomes
  • Membrane Glycoproteins
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Models, Genetic
  • Mutation
  • Peripheral Nervous System Diseases
  • Phenotype
  • Receptors, Scavenger
  • Recombination, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins
  • Subcellular Fractions
  • Time Factors
  • Tissue Distribution
  • Transgenes
  • Ureter
  • Urinary Bladder
  • Urothelium