Mouse Genome Informatics
hm
    Clcn6tm1Tjj/Clcn6tm1Tjj
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Characterization of storage material and axonal swelling in Clcn6tm1Tjj/Clcn6tm1Tjj mice

cellular
• starting at 4 weeks and becoming strong at >3 months in the cortex, autofluorescence of neurons in virtually all brain regions is detected, resulting from lipofuscin accumulation in initial axon segments of neurons; accumulation increases with age

behavior/neurological
• mutants spend less time spent in center of elevated plus maze and number of open-arm entries is reduced in mutants
• mice spend more time in center of test arena, indicating decrease in anxiety
• mutants spend less time in vertical exploratory behavior, as measured by decreased vertical rearings
• mutants show doubled tail-flick latencies compared to wild-type

nervous system
• neurons in the brain show autofluorescence resulting from accumulation of lipofuscin
• soma of cortical neurons show reduced cathepsin D which is concentrated in proximal axons instead; other lysosomal markers are mislocalized in mutants vs wild-type
• cortical neurons frequently show enlargements of the proximal axons, due to lipopigment deposits; deposits consist of lipid droplets associated with amorphous or granular material
• DRG axons have abundant storage material including curvilinear storage bodies and fingerprints
• granular osmophilic deposits (GRODs) in proximal axons contain mitochondrial ATP synthase and lysosomal proteins

integument
• mutants show doubled tail-flick latencies compared to wild-type

Mouse Models of Human Disease
OMIM IDRef(s)
Ceroid Lipofuscinosis, Neuronal, 3; CLN3 204200 J:113752