Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N11p Generation Definitions

Appearance
black
Related Genotype: a/a

Description
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 Pdeb^rd1 .

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Cln6^nclf allele

003602	B6 x STOCK Cln6nclf-Edardl-3J/J
002648	STOCK a/a Cln6nclf/J

View Strains carrying   Cln6^nclf     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- 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).

Ceroid Lipofuscinosis, Neuronal, 6; CLN6

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive; CLN4A   (CLN6)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Cln6^nclf/Cln6^nclf

        involves: C57BL/6J * C57BL/10J * C3HeB/FeJLe

• mortality/aging
• premature death   (MGI Ref ID J:47292)
• behavior/neurological phenotype
• paralysis
  • paresis progresses to paralysis typically by 9 months of age   (MGI Ref ID J:47292)
  • paralysis is spastic in nature   (MGI Ref ID J:47292)
• paresis
  • develop rear limb paresis by 8 months of age   (MGI Ref ID J:47292)
  • paresis is spastic in nature   (MGI Ref ID J:47292)
• seizures
  • terminal seizures have been seen   (MGI Ref ID J:47292)
• nervous system phenotype
• abnormal myelination
  • many profiles of degenerating myelin sheaths and axons are seen in the white matter of the spinal cord   (MGI Ref ID J:47292)
  • lesions in the spinal cord are consistent with Wallerian degeneration   (MGI Ref ID J:47292)
• abnormal neuron physiology
  • 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   (MGI Ref ID J:47292)
  • amount of inclusion material increases with age   (MGI Ref ID J:47292)
• astrocytosis
  • by 6 months of age increasing numbers of hypertrophic astrocytes are seen in the cerebral cortex, thalamus and brain stem indicative of reactive gliosis   (MGI Ref ID J:47292)
• axon degeneration
  • many profiles of degenerating myelin sheaths and axons are seen in the white matter of the spinal cord   (MGI Ref ID J:47292)
  • lesions in the spinal cord are consistent with Wallerian degeneration   (MGI Ref ID J:47292)
  • however, no necrotic or apoptotic nuclei are detected in the central nervous system   (MGI Ref ID J:47292)
• seizures
  • terminal seizures have been seen   (MGI Ref ID J:47292)
• vision/eye phenotype
• retinal degeneration
  • begins around 4 months of age   (MGI Ref ID J:47292)
  • by 5 - 6 months of age, the outer nuclear layer is reduced to 5-6 cell layers compared to 11 in controls   (MGI Ref ID J:47292)

View Research Applications

Research Applications

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

Cln6^nclf related

Neurobiology Research
Ataxia (Movement) Defects
Myelination Defects
Neurodegeneration
Neuromuscular Defects

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information provided by MGI

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; CLN4A; D9Bwg1455e; DNA segment, Chr 9, Brigham & Women's Genetics 1455 expressed; HsT18960; RIKEN cDNA 1810065L06 gene; expressed sequence AW743417; nclf; neuronal ceroid lipofuscinosis;
Molecular Note		This allele comprises 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. [MGI Ref ID J:73921] [MGI Ref ID J:73923]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

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]

Cln6^nclf related

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]

Chang B; Hawes NL; Hurd RE; Wang J; Howell D; Davisson MT; Roderick TH; Nusinowitz S; Heckenlively JR. 2005. Mouse models of ocular diseases. Vis Neurosci 22(5):587-93. [PubMed: 16332269]  [MGI Ref ID J:156373]

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]

Kielar C; Wishart TM; Palmer A; Dihanich S; Wong AM; Macauley SL; Chan CH; Sands MS; Pearce DA; Cooper JD; Gillingwater TH. 2009. Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum Mol Genet 18(21):4066-80. [PubMed: 19640925]  [MGI Ref ID J:153101]

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]

Staropoli JF; Haliw L; Biswas S; Garrett L; Holter SM; Becker L; Skosyrski S; Da Silva-Buttkus P; Calzada-Wack J; Neff F; Rathkolb B; Rozman J; Schrewe A; Adler T; Puk O; Sun M; Favor J; Racz I; Bekeredjian R; Busch DH; Graw J; Klingenspor M; Klopstock T; Wolf E; Wurst W; Zimmer A; Lopez E; Harati H; Hill E; Krause DS; Guide J; Dragileva E; Gale E; Wheeler VC; Boustany RM; Brown DE; Breton S; Ruether K; Gailus-Durner V; Fuchs H; de Angelis MH; Cotman SL. 2012. Large-scale phenotyping of an accurate genetic mouse model of JNCL identifies novel early pathology outside the central nervous system. PLoS One 7(6):e38310. [PubMed: 22701626]  [MGI Ref ID J:187839]

Thelen M; Damme M; Schweizer M; Hagel C; Wong AM; Cooper JD; Braulke T; Galliciotti G. 2012. Disruption of the autophagy-lysosome pathway is involved in neuropathology of the nclf mouse model of neuronal ceroid lipofuscinosis. PLoS One 7(4):e35493. [PubMed: 22536393]  [MGI Ref ID J:187205]

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]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• View the complete collection of spontaneous mutants in the Mouse Mutant Resource.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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