Related Experiment Video
Updated: Sep 30, 2026

A Simple Mechanical Procedure to Create Limbal Stem Cell Deficiency in Mouse
Published on: November 17, 2016
CLC-3 deficiency leads to phenotypes similar to human neuronal ceroid lipofuscinosis
Momono Yoshikawa1, Shinichi Uchida, Junji Ezaki
1Homeostasis Medicine and Nephrology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo Tokyo 113-8519, Japan.
Background:
CLC-3 is a member of the CLC chloride channel family and is widely expressed in mammalian tissues. To determine the physiological role of CLC-3, we generated CLC-3-deficient mice (Clcn3-/- ) by targeted gene disruption.
Results:
Together with developmental retardation and higher mortality, the Clcn3-/- mice showed neurological manifestations such as blindness, motor coordination deficit, and spontaneous hyperlocomotion. In histological analysis, the Clcn3-/- mice showed a pattern of progressive degeneration of the retina, hippocampus and ileal mucosa, which resembled the phenotype observed in cathepsin D knockout mice. The defect of cathepsin D results in a lysosomal accumulation of ceroid lipofuscin containing the mitochondrial F1F0 ATPase subunit c. In immunohistochemistry and Western blot analysis, we found that the subunit c was heavily accumulated in the lysosome of Clcn3-/- mice. Furthermore, we detected an elevation in the endosomal pH of the Clcn3-/- mice.
Conclusions:
These results indicated that the neurodegeneration observed in the Clcn3-/- mice was caused by an abnormality in the machinery which degrades the cellular protein and was associated with the phenotype of neuronal ceroid lipofuscinosis (NCL). The elevated endosomal pH could be an important factor in the pathogenesis of NCL.
Related Concept Videos
Lysosomal Hydrolases
Neural Regulation
Pleiotropy
Genetic Lingo
Cardiomyopathy III: Hypertrophic Cardiomyopathy
Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
