Phenotypes associated with this allele

• Allele Symbol: Cln3^tm1.1Mem
• Allele Name: targeted mutation 1.1, Marcy MacDonald
• Allele ID: MGI:2388888
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cln3^tm1.1Mem/Cln3^tm1.1Mem	involves: 129S/SvEv * CD-1	MGI:3044770

Genotype
MGI:3044770

hm1

• Allelic Composition: Cln3^tm1.1Mem/Cln3^tm1.1Mem
• Genetic Background: involves: 129S/SvEv * CD-1

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

mortality/aging

premature death ( J:79615 )

• homozygotes show reduced (80%) survival, with the earliest death occurring at 7 months of age

behavior/neurological

behavior/neurological phenotype ( J:79615 )

N • no handling-induced seizures are observed

limb grasping ( J:79615 )

• at 10-12 months, tail hang/clasping assays revealed clasping in 42% of homozygous mutant mice, compared with 10% of wild-type or heterozygous mutant mice

abnormal gait ( J:79615 )

• at 10-12 months, gait analyses indicated shortened average stride length (rear paw) and increased base width (rear paw stance)

short stride length ( J:79615 )

• at 10 -12 months of age

liver/biliary system

abnormal hepatocyte morphology ( J:79615 )

• in liver, ATP synthase subunit c-reactive deposition is observed as early as E19.5

• at 10 months, mutant hepatocytes contain abundant autofluorescent, ATP synthase subunit c-reactive membrane deposits

vision/eye

abnormal retina neuronal layer morphology ( J:79615 )

• retinal neurons contain membrane deposits in the RGC layer and the inner nuclear layer (INL), with small punctate granules in the outer nuclear layer (ONL)

• retinal deposits are first observed at P1.5, within the neuroblastic layer

• punctate subunit c-reactive granules are noted within the ONL and INL in the mature retina at P8 and P30

decreased retina photoreceptor cell number ( J:79615 )

• at 10-17 months, retinas of hypopigmented homozygotes show a 37% reduction in the number of cone cells per field relative to retinas of hypopigmented heterozygotes

abnormal retina ganglion cell morphology ( J:79615 )

• retinal ganglion cells show electron-dense membranous perinuclear inclusions with a JNCL-like 'fingerprint' profile

retina degeneration ( J:79615 )

• retinas from pigmented homozygotes do not exhibit a cone cell loss at 10-17 months, suggesting that hypopigmentation may accelerate retinal degeneration

nervous system

abnormal nervous system morphology ( J:79615 )

• at 10 months, homozygotes display membranous deposits in the CNS

• autofluorescent, ATP synthase subunit c-reactive membrane deposits are observed in the cytoplasm of CA2 and CA3 pyramidal cells of the hippocampus, Purkinje cells of the cerebellum, as well as cortical neurons and thalamic neurons

abnormal dentate gyrus morphology ( J:79615 )

• accumulates are first noted at E19.5 in neurons of the dentate gyrus and in the subventricular zone at the lateral ventricle

• in these regions, ATP synthase subunit c-reactive deposits are undetectable after P8

abnormal hippocampus pyramidal cell morphology ( J:79615 )

• ultrastructurally, CA2/3 hippocampal pyramidal neurons show abundant perinuclear, osmiophilic and electron-dense inclusions

• such subunit-c inclusions have multilamellar membranes, a JNCL-like 'fingerprint' appearance, and are first detected at P8, increasing in size and intensity by P30

abnormal cerebellar Purkinje cell layer ( J:79615 )

• cerebellar deposits are detected in the Purkinje cell layer at E19.5, increasing in severity by P30

abnormal postnatal subventricular zone morphology ( J:79615 )

• accumulates are first noted at E19.5 in neurons of the dentate gyrus and in the subventricular zone at the lateral ventricle

• in these regions, ATP synthase subunit c-reactive deposits are undetectable after P8

gliosis ( J:79615 )

• at 10 months, all homozygotes exhibit reactive gliosis in the motor cortex, white matter tracts of the cerebellum and midbrain, including the inferior colliculus

• no apoptotic changes are observed in these regions

decreased retina photoreceptor cell number ( J:79615 )

• at 10-17 months, retinas of hypopigmented homozygotes show a 37% reduction in the number of cone cells per field relative to retinas of hypopigmented heterozygotes

abnormal retina ganglion cell morphology ( J:79615 )

• retinal ganglion cells show electron-dense membranous perinuclear inclusions with a JNCL-like 'fingerprint' profile

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 3		DOID:0110731	OMIM:204200	J:79615