Phenotypes Associated with This Genotype

Genotype
MGI:3688436

• Allelic Composition: Clcn6^tm1Tjj/Clcn6^tm1Tjj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Characterization of storage material and axonal swelling in Clcn6^tm1Tjj/Clcn6^tm1Tjj mice

cellular

lysosomal protein accumulation ( J:113752 )

• 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

abnormal anxiety-related response ( J:113752 )

• mutants spend less time spent in center of elevated plus maze and number of open-arm entries is reduced in mutants

decreased anxiety-related response ( J:113752 )

• mice spend more time in center of test arena, indicating decrease in anxiety

decreased vertical activity ( J:113752 )

• mutants spend less time in vertical exploratory behavior, as measured by decreased vertical rearings

increased thermal nociceptive threshold ( J:113752 )

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

nervous system

abnormal neuron morphology ( J:113752 )

• 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

abnormal axon morphology ( J:113752 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 3		DOID:0110731	OMIM:204200	J:113752