Overview

Also Known As:motor neuron degeneration

This strain is currently unavailable due to replenishing of cryopreserved stocks.

These mice carry a spontaneous mutation at the Cln8 locus characterized by hindlimb weakness, ataxia, and early death.

Genetic overview

Genetic Background	Generation

Cln8^mnd

Allele Type	Gene Symbol	Gene Name
Spontaneous	Cln8	ceroid-lipofuscinosis, neuronal 8

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Research Applications

Neurobiology Research
Sensorineural Research

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Details

Detailed Description

Mice homozygous for the motor neuron degeneration (mnd) spontaneous mutation show onset of disease between 5 and 11 months. Disease characterics include hindlimb weakness and ataxia which progresses to severe spastic paralysis of all limbs, with death usually by 9 to 14 months. Histological examination of the nervous system of affected animals shows sudanophyllic, autofluorescent intraneuronal inclusions characteristic of human neuronal ceroid lipofuscinosis suggesting that mnd mice are models for such human disease as Batten's disease. Performance at 14-16 weeks of age in an associative learning task is significantly decreased relative to controls, thus providing an early disease phenotype for this neuronal ceroid lipofuscinosis model. (Wendt KD, et al., 2005) Males and females are equally affected and both are fertile, although breeding efficiency is reduced.

Homozygous mnd mice exhibit a retinopathy characterized by an early and progressive degeneration which primarily involves loss of photoreceptor cells and subsequently affects retinal neuronal cells (Guarneri R et al., 2004).

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Bronson RT; Lake BD; Cook S; Taylor S; Davisson MT. 1993. Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten's disease). Ann Neurol 33(4):381-5PubMed: 7683855 MGI: J:12816
Messer A; Flaherty L. 1986. Autosomal dominance in a late-onset motor neuron disease in the mouse. J Neurogenet 3(6):345-55PubMed: 3783318 MGI: J:8492
Messer A; Plummer J; Maskin P; Coffin JM; Frankel WN. 1992. Mapping of the motor neuron degeneration (Mnd) gene, a mouse model of amyotrophic lateral sclerosis (ALS). Genomics 13(3):797-802PubMed: 1639406 MGI: J:1224

View All References

Genetics

Cln8^mnd

Allele Symbol: Cln8^mnd

Allele Name	motor neuron degeneration
Allele Type	Spontaneous
Allele Synonym(s)	Cln8mnd; mnd
Gene Symbol and Name	Cln8, ceroid-lipofuscinosis, neuronal 8
Gene Synonym(s)
Strain of Origin	B6.KB2-H2^b5
Chromosome	8
General Note	Early papers (J:8492, J:1224) state that this allele exhibits phenotypic similarity to amytrophic lateral sclerosis (ALS), however further analysis (J:12816, 56219) revealed that it is a better model for neuronal ceroid lipofuscinoses (Batten's disease) than for ALS.
Molecular Note	A single nucleotide insertion (267-268C, codon 90) predicts a frameshift and a truncated protein.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

neuronal ceroid lipofuscinosis 8

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Cln8^mnd related

Neurobiology Research
- Ataxia (Movement) Defects
- Behavioral and Learning Defects
- Metabolic Defects
- Neurodegeneration
- Neuromuscular defects
Sensorineural Research
- Retinal Degeneration

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Cln8^mnd/Cln8^mnd
involves: B6.KB2 * C3H/HeJ

mortality/aging

premature death
- Background Sensitivity - death similar to that seen on the inbred B6.KB2 background

nervous system phenotype

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

abnormal nervous system morphology
- Background Sensitivity - neurological disease progresses in a similar fashion as on the inbred B6.KB2 background

Genotype: Cln8^mnd/Cln8^mnd
involves: AKR/J * B6.KB2

vision/eye phenotype

abnormal retinal photoreceptor layer morphology

abnormal retinal rod cell inner segment morphology
- rapid thinning of the rod inner segment layer by P25, with a more gradual thinning at later stages

abnormal retinal rod cell outer segment morphology
- rapid thinning of the rod outer segment layer by P25, with a more gradual thinning at later stages

thin retinal outer nuclear layer
- 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

retinal degeneration
- detectable at P15 and more pronounced with age

abnormal retinal pigment epithelium morphology
- focal thinning of the retinal pigment epithelium occurs at late stages of degeneration

short photoreceptor outer segment
- progressive shortening of the outer segments while maintaining relatively normal structure

short photoreceptor inner segment
- at very late stages of degeneration, inner segments are shortened and broadened

mortality/aging

premature death
- Background Sensitivity - death by 7 months of age, compared to 9-14 months on the inbred B6.KB2 background

nervous system phenotype

abnormal retinal rod cell inner segment morphology
- rapid thinning of the rod inner segment layer by P25, with a more gradual thinning at later stages

short photoreceptor outer segment
- progressive shortening of the outer segments while maintaining relatively normal structure

abnormal motor neuron morphology
- 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 retinal rod cell outer segment morphology
- rapid thinning of the rod outer segment layer by P25, with a more gradual thinning at later stages

short photoreceptor inner segment
- at very late stages of degeneration, inner segments are shortened and broadened

abnormal nervous system morphology
- 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

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- focal thinning of the retinal pigment epithelium occurs at late stages of degeneration

Genotype: Cln8^mnd/Cln8^mnd
AK.B6(Cg)-Cln8

mortality/aging

premature death
- Background Sensitivity - die by 5.5 months of age

nervous system phenotype

abnormal motor neuron morphology
- 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

The following phenotype relates to a compound genotype created using this strain

Genotype: Cln8^mnd/Cln8^mnd
B6.KB2/Rn-Cln8

nervous system phenotype

abnormal motor neuron morphology
- Background Sensitivity - exhibit motor neuron disease symptoms at around 6 months of age
- motor neurons have eccentric or indiscrete nuclei, disrupted membranes and shape changes
- inclusion bodies containing ubiquitin were found in spinal neurons of mnd mice, even prior to onset of symptoms

abnormal spinal cord ventral horn morphology
- degeneration of anterior horn cells in the spinal cord

motor neuron degeneration
- 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
- degeneration of cranial nerves

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

abnormal hypoglossal nerve morphology
- degenerating

abnormal vagus nerve morphology
- degenerating dorsal motor vagus

reproductive system phenotype

decreased litter size
- lower number of progeny/litter and lower numbers of total litters

vision/eye phenotype

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

abnormal retinal photoreceptor layer morphology
- atrophy of the photoreceptor layer in mice older than 3 months and nearly complete loss of this layer by 8 months of age

behavior/neurological phenotype

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

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

limb grasping

abnormal locomotor behavior
- unable to walk uphill
- dragging or splaying of the hindlimbs while walking

paresis
- begin to develop paresis by 6 months of age

abnormal motor capabilities/coordination/movement
- hindlimbs are unable to grasp the bars of wire cagetop when attempting to walk over it

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

mortality/aging

premature death
- Background Sensitivity - most die by 9-14 months of age

Genotype: Cln8^mnd/Cln8⁺
involves: B6.KB2 * C57BL/6Fla

nervous system phenotype

abnormal motor neuron morphology
- exhibit neurological disease, with onset of mild symptoms at an age (5 months) similar to homozygotes
- 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.
- slower emergence of more severe motor neuron disease symptoms than in homozygotes

Genotype: Cln8^mnd/Cln8^mnd
involves: B6.KB2

behavior/neurological phenotype

seizures
- terminal seizures have been seen

nervous system phenotype

abnormal myelination
- lesions in the spinal cord are consistent with Wallerian degeneration
- many profiles of degenerating myelin sheaths and axons are seen in the white matter of the spinal cord

axon degeneration
- lesions in the spinal cord are consistent with Wallerian degeneration
- many profiles of degenerating myelin sheaths and axons are seen in the white matter of the spinal cord
- Normal - however, no necrotic or apoptotic nuclei are detected in the central nervous system

gliosis

seizures
- terminal seizures have been seen

References

Bronson RT; Lake BD; Cook S; Taylor S; Davisson MT. 1993. Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten's disease). Ann Neurol 33(4):381-5PubMed: 7683855 MGI: J:12816
Messer A; Flaherty L. 1986. Autosomal dominance in a late-onset motor neuron disease in the mouse. J Neurogenet 3(6):345-55PubMed: 3783318 MGI: J:8492
Messer A; Plummer J; Maskin P; Coffin JM; Frankel WN. 1992. Mapping of the motor neuron degeneration (Mnd) gene, a mouse model of amyotrophic lateral sclerosis (ALS). Genomics 13(3):797-802PubMed: 1639406 MGI: J:1224

Additional References

Chang B; Hawes NL; Hurd RE; Davisson MT; Nusinowitz S; Heckenlively JR. 2002. Retinal degeneration mutants in the mouse. Vision Res 42(4):517-25PubMed: 11853768 MGI: J:75095
Guarneri R; Russo D; Cascio C; D'Agostino S; Galizzi G; Bigini P; Mennini T; Guarneri P. 2004. Retinal oxidation, apoptosis and age- and sex-differences in the mnd mutant mouse, a model of neuronal ceroid lipofuscinosis. Brain Res 1014(1-2):209-20PubMed: 15213005 MGI: J:90947
Mazurkiewicz JE. 1991. Ubiquitin deposits are present in spinal motor neurons in all stages of the disease in the motor neuron degeneration (Mnd) mutant of the mouse. Neurosci Lett 128(2):182-6PubMed: 1658691 MGI: J:624
Messer A; Plummer J; MacMillen MC; Frankel WN. 1995. Genetics of primary and timing effects in the mnd mouse. Am J Med Genet 57(2):361-4PubMed: 7668363 MGI: J:25748
Messer A; Plummer J; Wong V; Lavail MM. 1993. Retinal degeneration in motor neuron degeneration (mnd) mutant mice [letter] Exp Eye Res 57(5):637-41PubMed: 8282051 MGI: J:19328

Additional - Cln8^mnd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Cln8
- Sanger sequencing:Cln8-alternate1
- Genotyping resources and troubleshooting
Appearance
- black, ataxic
  Related Genotype: a/a Cln8^mnd/Cln8^mnd
Citation
When using the motor neuron degeneration mouse strain in a publication, please cite the originating article(s) and include JAX stock #001612 in your Materials and Methods section.

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Email: TechTran@jax.org

Also Known As:motor neuron degeneration

Genetic overview

Research Applications

Detailed Description

Control Suggestions

Additional Information

Selected References

Cln8mnd

Allele Symbol: Cln8mnd

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Cln8mnd related

Mammalian Phenotype Terms by Genotype

Genotype: Cln8mnd/Cln8mndinvolves: B6.KB2 * C3H/HeJ

mortality/aging

nervous system phenotype

Genotype: Cln8mnd/Cln8mndinvolves: AKR/J * B6.KB2

vision/eye phenotype

mortality/aging

nervous system phenotype

pigmentation phenotype

Genotype: Cln8mnd/Cln8mndAK.B6(Cg)-Cln8

mortality/aging

nervous system phenotype

Genotype: Cln8mnd/Cln8mndB6.KB2/Rn-Cln8

nervous system phenotype

reproductive system phenotype

vision/eye phenotype

behavior/neurological phenotype

mortality/aging

Genotype: Cln8mnd/Cln8+involves: B6.KB2 * C57BL/6Fla

nervous system phenotype

Genotype: Cln8mnd/Cln8mndinvolves: B6.KB2

behavior/neurological phenotype

nervous system phenotype

References

Additional References

Additional - Cln8mnd related

Genotyping Protocols

Appearance

Citation

Strain Interest Registration

Contact Information

Interest

Terms Of Use

Licensing Information

Cln8^mnd

Allele Symbol: Cln8^mnd

Genotype: Cln8^mnd related

Genotype: Cln8^mnd/Cln8^mnd
involves: B6.KB2 * C3H/HeJ

Genotype: Cln8^mnd/Cln8^mnd
involves: AKR/J * B6.KB2

Genotype: Cln8^mnd/Cln8^mnd
AK.B6(Cg)-Cln8

Genotype: Cln8^mnd/Cln8^mnd
B6.KB2/Rn-Cln8

Genotype: Cln8^mnd/Cln8⁺
involves: B6.KB2 * C57BL/6Fla

Genotype: Cln8^mnd/Cln8^mnd
involves: B6.KB2

Additional - Cln8^mnd related