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Type Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N11p Appearance
black
Related Genotype: a/aDescription
Mice homozygous for the neuronal ceroid lipofuscinosis mutation (nclf) have a phenotype that is very similar to mice homozygous for the motor neuron degeneration mutation (mnd). Homozygous mutant mice display abnormal proteolipid storage by lysosomes termed neuronal ceroid lipofuscinosis. Mice also develop progressive retinal degeneration at an early age. Affected neuronal lysosomes show abnormal morphology. Severe cerebral gliosis and Wallerian degeneration of long neuronal tracts occur late in the disease and account for the motor neuron abnormalities and eventual paralysis. Homozygotes live to approximately 9 months of age.Development
The nclf mutation was discovered in 1991 at The Jackson Laboratory in a colony of mice of mixed C57BL/6J, C57BL/10J and C3Heb/FeJLe-a/a background carrying the juvenile bare (jb) mutation. The neurological phenotype was lost from the jb stock as inbreeding progressed, but fortunately, embryos had been preserved before nclf was bred out of the stock. nclf was backcrossed onto C57BL/6J to determine whether this mutation causes retinal degeneration in the absence of the C3H-derived Pdebrd1 .
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying Cln6nclf allele
003602 B6 x STOCK Cln6nclf-Edardl-3J/J 002648 STOCK a/a Cln6nclf/J View Strains carrying Cln6nclf (2 strains)
Congenic Nomenclature
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms
Ceroid Lipofuscinosis, Neuronal, 6; CLN6 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Cln6nclf/Cln6nclf
involves: C57BL/6J * C57BL/10J * C3HeB/FeJLe
- life span-post-weaning/aging
- premature death (MGI Ref ID J:47292)
- behavior/neurological phenotype
- paralysis (MGI Ref ID J:47292)
- paresis progresses to paralysis typically by 9 months of age
- paralysis is spastic in nature
- paresis (MGI Ref ID J:47292)
- develop rear limb paresis by 8 months of age
- paresis is spastic in nature
- seizures (MGI Ref ID J:47292)
- terminal seizures have been seen
- nervous system phenotype
- abnormal myelination (MGI Ref ID 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
- abnormal neuron physiology (MGI Ref ID J:47292)
- at 11 days of age, accumulation of luxol fast blue staining material is seen in inclusions in neurons in all parts of the brain and spinal cord
- amount of inclusion material increases with age
- astrocytosis (MGI Ref ID J:47292)
- by 6 months of age increasing numbers of hypertrophic astrocytes are seen in the cerebral cortex, thalamus and brain stem indicative of reactive gliosis
- axon degeneration (MGI Ref ID 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
- seizures (MGI Ref ID J:47292)
- terminal seizures have been seen
- vision/eye phenotype
- retinal degeneration (MGI Ref ID J:47292)
- begins around 4 months of age
- by 5 - 6 months of age, the outer nuclear layer is reduced to 5-6 cell layers compared to 11 in controls
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Cln6nclf related
Neurobiology Research
Ataxia (Movement) Defects
Myelination Defects
Neurodegeneration
Neuromuscular Defects
Sensorineural Research
Retinal Degeneration
| Allele Symbol | Cln6nclf | ||
|---|---|---|---|
| Allele Name | neuronal ceroid lipofuscinosis | ||
| Allele Type | Spontaneous | ||
| Common Name(s) | nclf; | ||
| Strain of Origin | Mixed stock | ||
| Gene Symbol and Name | Cln6, ceroid-lipofuscinosis, neuronal 6 | ||
| Chromosome | 9 | ||
| Gene Common Name(s) | 1810065L06Rik; AW743417; D9Bwg1455e; DNA segment, Chr 9, Brigham & Women's Genetics 1455 expressed; FLJ20561; HsT18960; RIKEN cDNA 1810065L06 gene; expressed sequence AW743417; nclf; neuronal ceroid lipofuscinosis; | ||
| General Note | Homozygous mutant mice develop progressive retinal atrophy at an early age. Luxol fast blue staining, indicative of proteolipid accumulation, occurs in cytoplasm of neurons and other types of cells. Affected lysosomes show abnormal morphology. Severe cerebral gliosis and Wallerian degeneration of long neuronal tracts occur late in the disease and account for the motor neuron abnormalities. Paralysis and death occur by around 9 months of age (J:47292). | ||
| Molecular Note | The underlying mutation responsible for the phenotype in the nclf mouse was identified as a single nucleotide insertion of a cysteine, located within a run of cysteines in exon four. The insertion produces a frameshift at amino acid 103, followed by a premature stop codon. Numerous mutations were identified in the human ortholog of families with variant late infantile ceroid lipofuscinosis. The identical mutation in the nclf mouse was observed in three families of Pakastani origin. [MGI Ref ID J:73921] [MGI Ref ID J:73923] | ||
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
Bronson RT; Donahue LR; Johnson KR; Tanner A; Lane PW; Faust JR. 1998. Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9. Am J Med Genet 77(4):289-97. [PubMed: 9600738] [MGI Ref ID J:47292]
Chang B; Hawes NL; Hurd RE; Davisson MT; Nusinowitz S; Heckenlively JR. 2002. Retinal degeneration mutants in the mouse. Vision Res 42(4):517-25. [PubMed: 11853768] [MGI Ref ID J:75095]
Gao H; Boustany RM; Espinola JA; Cotman SL; Srinidhi L; Antonellis KA; Gillis T; Qin X; Liu S; Donahue LR; Bronson RT; Faust JR; Stout D; Haines JL; Lerner TJ; MacDonald ME. 2002. Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse. Am J Hum Genet 70(2):324-35. [PubMed: 11791207] [MGI Ref ID J:73923]
Wheeler RB; Sharp JD; Schultz RA; Joslin JM; Williams RE; Mole SE. 2002. The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein. Am J Hum Genet 70(2):537-42. [PubMed: 11727201] [MGI Ref ID J:73921]
Cln6nclf relatedBronson RT; Donahue LR; Johnson KR; Tanner A; Lane PW; Faust JR. 1998. Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9. Am J Med Genet 77(4):289-97. [PubMed: 9600738] [MGI Ref ID J:47292]
Chang B; Hawes NL; Hurd RE; Davisson MT; Nusinowitz S; Heckenlively JR. 2002. Retinal degeneration mutants in the mouse. Vision Res 42(4):517-25. [PubMed: 11853768] [MGI Ref ID J:75095]
Gao H; Boustany RM; Espinola JA; Cotman SL; Srinidhi L; Antonellis KA; Gillis T; Qin X; Liu S; Donahue LR; Bronson RT; Faust JR; Stout D; Haines JL; Lerner TJ; MacDonald ME. 2002. Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse. Am J Hum Genet 70(2):324-35. [PubMed: 11791207] [MGI Ref ID J:73923]
Jabs S; Quitsch A; Kakela R; Koch B; Tyynela J; Brade H; Glatzel M; Walkley S; Saftig P; Vanier MT; Braulke T. 2008. Accumulation of bis(monoacylglycero)phosphate and gangliosides in mouse models of neuronal ceroid lipofuscinosis. J Neurochem 106(3):1415-25. [PubMed: 18498441] [MGI Ref ID J:138648]
Pohl S; Mitchison HM; Kohlschutter A; van Diggelen O; Braulke T; Storch S. 2007. Increased expression of lysosomal acid phosphatase in CLN3-defective cells and mouse brain tissue. J Neurochem 103(6):2177-88. [PubMed: 17868323] [MGI Ref ID J:128711]
Wheeler RB; Sharp JD; Schultz RA; Joslin JM; Williams RE; Mole SE. 2002. The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein. Am J Hum Genet 70(2):537-42. [PubMed: 11727201] [MGI Ref ID J:73921]
Currently there no information available for this strain. This may be due to the supply level of this strain.
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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