Description

Strain Information

Type Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N11p

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)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

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.

Cln6^nclf/Cln6^nclf

        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:

Cln6^nclf related

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

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information

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]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	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.

General Terms and Conditions

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The Jackson Laboratory's Genotype Promise

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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fax:	207-288-6655

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