Phenotypes associated with this allele

• Allele Symbol: Cln8^mnd
• Allele Name: motor neuron degeneration
• Allele ID: MGI:1856959
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cln8^mnd/Cln8^mnd	AK.B6(Cg)-Cln8^mnd	MGI:3588732
hm2	Cln8^mnd/Cln8^mnd	B6.KB2/Rn-Cln8^mnd	MGI:2388398
hm3	Cln8^mnd/Cln8^mnd	involves: AKR/J * B6.KB2	MGI:2388401
hm4	Cln8^mnd/Cln8^mnd	involves: B6.KB2	MGI:3810164
hm5	Cln8^mnd/Cln8^mnd	involves: B6.KB2 * C3H/HeJ	MGI:3588731
ht6	Cln8^mnd/Cln8^+	involves: B6.KB2 * C57BL/6Fla	MGI:3588673

Genotype
MGI:3588732

hm1

• Allelic Composition: Cln8^mnd/Cln8^mnd
• Genetic Background: AK.B6(Cg)-Cln8^mnd

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

mortality/aging

premature death ( J:56219 )

• Background Sensitivity: die by 5.5 months of age

nervous system

abnormal motor neuron morphology ( J:56219 )

• Background Sensitivity: motor neuron disease is accelerated even more than in the mixed AKR/J and B6.KB2 background, with symptoms appearing by 4 months and death by 5.5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 8		DOID:0110723	OMIM:600143	J:56219

Genotype
MGI:2388398

hm2

• Allelic Composition: Cln8^mnd/Cln8^mnd
• Genetic Background: B6.KB2/Rn-Cln8^mnd

mortality/aging

premature death ( J:8492 , J:56219 )

• Background Sensitivity: most die by 9-14 months of age (J:8492)

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:8492 )

• hindlimbs are unable to grasp the bars of wire cagetop when attempting to walk over it

limb grasping ( J:8492 )

abnormal locomotor behavior ( J:8492 )

• unable to walk uphill

• dragging or splaying of the hindlimbs while walking

ataxia ( J:8492 )

• age of onset is approximately 5- 11 months of age, progressive with age

paralysis ( J:12816 )

• progress to severe spastic paresis and paralysis by 9 months of age

hindlimb paralysis ( J:8492 )

• age of onset is approximately 5- 11 months of age, progressive with age

paresis ( J:12816 )

• begin to develop paresis by 6 months of age

nervous system

abnormal nervous system morphology ( J:12816 )

• contain LFB-positive intracytoplasmic inclusion material in most neurons in virtually all parts of the brain and spinal cord unlike in controls

abnormal motor neuron morphology ( J:8492 , J:56219 )

• inclusion bodies containing ubiquitin were found in spinal neurons of mnd mice, even prior to onset of symptoms (J:8492)

• motor neurons have eccentric or indiscrete nuclei, disrupted membranes and shape changes (J:8492)

• Background Sensitivity: exhibit motor neuron disease symptoms at around 6 months of age (J:56219)

motor neuron degeneration ( J:8492 )

• degeneration of the upper and lower motor neurons of the spinal cord and cranial nerves and of some areas of the brain

abnormal cranial nerve morphology ( J:8492 )

• degeneration of cranial nerves

abnormal hypoglossal nerve morphology ( J:8492 )

• degenerating

abnormal vagus nerve morphology ( J:8492 )

• degenerating dorsal motor vagus

abnormal spinal cord ventral horn morphology ( J:8492 )

• degeneration of anterior horn cells in the spinal cord

reproductive system

decreased litter size ( J:8492 )

• lower number of progeny/litter and lower numbers of total litters

vision/eye

abnormal retina photoreceptor layer morphology ( J:12816 )

• atrophy of the photoreceptor layer in mice older than 3 months and nearly complete loss of this layer by 8 months of age

blindness ( J:12816 )

• begin to become blind by 2 months of age and by 5 months, are completely blind

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 8		DOID:0110723	OMIM:600143	J:12816 , J:56219

Genotype
MGI:2388401

hm3

• Allelic Composition: Cln8^mnd/Cln8^mnd
• Genetic Background: involves: AKR/J * B6.KB2

mortality/aging

premature death ( J:1224 , J:56219 )

• Background Sensitivity: death by 7 months of age, compared to 9-14 months on the inbred B6.KB2 background (J:1224)

vision/eye

abnormal retina pigment epithelium morphology ( J:19328 )

• focal thinning of the retinal pigment epithelium occurs at late stages of degeneration

thin retina outer nuclear layer ( J:19328 )

• at P15, the outer nuclear layer (ONL) contains greater number of pyknotic nuclei and is thinner

• rapid thinning of the ONL by P25, with a more gradual thinning at later ages

abnormal retina photoreceptor layer morphology ( J:19328 )

abnormal retina rod cell inner segment morphology ( J:19328 )

• rapid thinning of the rod inner segment layer by P25, with a more gradual thinning at later stages

short photoreceptor inner segment ( J:19328 )

• at very late stages of degeneration, inner segments are shortened and broadened

short photoreceptor outer segment ( J:19328 )

• progressive shortening of the outer segments while maintaining relatively normal structure

abnormal retina rod cell outer segment morphology ( J:19328 )

• rapid thinning of the rod outer segment layer by P25, with a more gradual thinning at later stages

increased susceptibility to age-related retinal degeneration ( J:19328 )

• detectable at P15 and more pronounced with age

pigmentation

abnormal retina pigment epithelium morphology ( J:19328 )

• focal thinning of the retinal pigment epithelium occurs at late stages of degeneration

nervous system

abnormal nervous system morphology ( J:1224 )

• Background Sensitivity: earlier age of onset (4.5-5 months) and increased speed of progression of neurological disease than on the inbred B6.KB2 background

abnormal motor neuron morphology ( J:56219 )

• Background Sensitivity: motor neuron disease is accelerated with 40% exhibiting symptoms by 4.5 months of age and dying by 6.5-7 months

abnormal retina rod cell inner segment morphology ( J:19328 )

• rapid thinning of the rod inner segment layer by P25, with a more gradual thinning at later stages

short photoreceptor inner segment ( J:19328 )

• at very late stages of degeneration, inner segments are shortened and broadened

short photoreceptor outer segment ( J:19328 )

• progressive shortening of the outer segments while maintaining relatively normal structure

abnormal retina rod cell outer segment morphology ( J:19328 )

• rapid thinning of the rod outer segment layer by P25, with a more gradual thinning at later stages

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 8		DOID:0110723	OMIM:600143	J:56219

Genotype
MGI:3810164

hm4

• Allelic Composition: Cln8^mnd/Cln8^mnd
• Genetic Background: involves: B6.KB2

nervous system

seizures ( J:47292 )

• terminal seizures have been seen

gliosis ( J:47292 )

axon degeneration ( J:47292 )

• many profiles of degenerating myelin sheaths and axons are seen in the white matter of the spinal cord

• lesions in the spinal cord are consistent with Wallerian degeneration

• however, no necrotic or apoptotic nuclei are detected in the central nervous system

abnormal myelination ( J:47292 )

• many profiles of degenerating myelin sheaths and axons are seen in the white matter of the spinal cord

• lesions in the spinal cord are consistent with Wallerian degeneration

behavior/neurological

seizures ( J:47292 )

• terminal seizures have been seen

Genotype
MGI:3588731

hm5

• Allelic Composition: Cln8^mnd/Cln8^mnd
• Genetic Background: involves: B6.KB2 * C3H/HeJ

mortality/aging

premature death ( J:1224 , J:56219 )

• Background Sensitivity: death similar to that seen on the inbred B6.KB2 background (J:1224)

nervous system

abnormal nervous system morphology ( J:1224 )

• Background Sensitivity: neurological disease progresses in a similar fashion as on the inbred B6.KB2 background

abnormal motor neuron morphology ( J:56219 )

• Background Sensitivity: exhibit motor neuron disease symptoms at around 6 months of age and do not die prior to 10-12 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 8		DOID:0110723	OMIM:600143	J:56219

Genotype
MGI:3588673

ht6

• Allelic Composition: Cln8^mnd/Cln8⁺
• Genetic Background: involves: B6.KB2 * C57BL/6Fla

nervous system

abnormal motor neuron morphology ( J:8492 , J:218228 )

• exhibit neurological disease, with onset of mild symptoms at an age (5 months) similar to homozygotes (J:8492)

• slower emergence of more severe motor neuron disease symptoms than in homozygotes (J:8492)

• NOTE: It was originally thought that heterozygoous mice as old as 18 months could be visually identified; however, it has been impossible to repeat these results- no histological pathology is detectable. (J:218228)