Strain Name:

FVB/N-Cers1to/J

Stock Number:

019483

Order this mouse

Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
The spontaneous mutant toppler is an allele of Lass1, a neuronally expressed ceramide synthase. Homozygotes exhibit progressive ataxia, Purkinje cell loss, and an accumulation of lipofuscin and may be useful for studies examining the role of lipid biosynthesis in neurodegenerative diseases.

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

Former Names FVB/N-Lass1to/J    (Changed: 22-JAN-13 )
Type Coisogenic; Mutant Strain; Spontaneous Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation+pN1
Generation Definitions
 
Donating Investigator Wendy Macklin,   University of Colorado

Description
Lass1 (LAG1 homolog, ceramide synthase 1) is a neuronally expressed enzyme that encodes (dihydro) ceramide synthase (CerS1). Ceramide functions as as a basic structural component of sphingolipids. Alterations in sphingolipid homeostasis are implicated in neurodegenerative disease. Toppler was identified as a C to A missense point mutation in exon 5 of the Lass1 gene. Mice homozygous for the spontaneous toppler mutation are viable and fertile. Beginning at 12-14 days, pups exhibit mild tremors when agitated. Tremors progress to ataxia and loss of balance. Mutant mice adopt a unique tripod stance using the hind limbs and tail as a base, while leaning against cage walls. Homozygotes exhibit reduced body size, a 25-50% decrease in cerebellum size, abnormal accumulation of lipofuscin, loss of Bergmann glia, and, between P21 and P30, a major loss of Purkinje cells. This mutant strain may be useful for studies examining the role of lipid biosynthesis in neurodegenerative diseases.

Development
The toppler (top) mutation arose spontaneously in a colony of FVB/N mice carrying a transgene expressing the neomycin resistance marker (pSVtkneo) in the laboratory of Dr. Wendy Macklin at the Cleveland Clinic Foundation in 2003. The mutation was identified in 4 female mice from a litter of 11 that exhibited ataxia and abnormal posturing. Subsequent outcrossing to (C3H x C57LB/6J)F1 and selection against the transgene indicated that the mutation was heritable and independent of the transgene. Mice then were transferred to the laboratory of Dr. Susan Ackerman at The Jackson Laboratory. Toppler was identified as a C to A missense point mutation in exon 5 of the Lass1 gene. The mutation alters the corresponding amino acid from aspartic acid to alanine at position 266. Dr. Macklin donated this strain to The Jackson Laboratory Repository in 2012. Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.

Control Information

  Control
   Wild-type from the colony
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Cers1to/Cers1to

        either: FVB/N or (involves: C3H * C57BL/6J * FVB/N)
  • mortality/aging
  • premature death
    • average life span is 8 - 10 months   (MGI Ref ID J:91243)
  • behavior/neurological phenotype
  • ataxia
    • mutants develop an ataxic gait around 14 days of age   (MGI Ref ID J:91243)
  • impaired balance
    • mutants develop severely impaired balance and are unable to stand erect needing to use a tripod stance when feeding, grooming, or nursing   (MGI Ref ID J:91243)
  • seizures
    • older mutants develop mild petit mal-type seizures   (MGI Ref ID J:91243)
  • tremors
    • mutants develop mild tremors by P12 that worsen with age and occur when the mutant is stationary or moving   (MGI Ref ID J:91243)
  • growth/size/body phenotype
  • decreased body weight
    • mutants are smaller compared to wild-type   (MGI Ref ID J:91243)
  • nervous system phenotype
  • Purkinje cell degeneration
    • Purkinje cell loss occurs between P21 and P30 so that by 6 months of age most lobules of the cerebellum have only a few remaining Purkinje cells   (MGI Ref ID J:91243)
  • abnormal Purkinje cell dendrite morphology
    • the dendritic arbors of Purkinje cells are shorter and thicker compared to wild-type   (MGI Ref ID J:91243)
  • decreased brain weight
    • the brain is smaller compared to wild-type   (MGI Ref ID J:91243)
  • gliosis
    • astrocytes appear to be increased in older mutants   (MGI Ref ID J:91243)
  • seizures
    • older mutants develop mild petit mal-type seizures   (MGI Ref ID J:91243)
  • small cerebellum
    • the cerebellum is smaller compared to wild-type although this may be a result of overall decreased body size   (MGI Ref ID J:91243)

Cers1to/Cers1to

        FVB/N-Cers1to
  • nervous system phenotype
  • abnormal Purkinje cell dendrite morphology
    • Purkinje cells exhibit higher order dendritic branching pattern abnormalities compared to in wild-type mice   (MGI Ref ID J:172719)
View Research Applications

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

Metabolism Research
Lipid Metabolism

Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects
      Purkinje cell defect
Neurodegeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Cers1to
Allele Name toppler
Allele Type Spontaneous
Common Name(s) to;
Strain of OriginFVB/N-Tg(TK-neo)#Doe
Gene Symbol and Name Cers1, ceramide synthase 1
Chromosome 8
Gene Common Name(s) LAG1; LAG1 homolog, ceramide synthase 1; LASS1; Lass1; UOG1; Uog-1; to; toppler;
Molecular Note A spontaneous C to A transition results in the amino acid substitution of aspartic acid for alanine at position 266 (A266D). [MGI Ref ID J:172719]

Genotyping

Genotyping Information

Genotyping Protocols

Lass1toPyro, Pyrosequencing


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Duchala CS; Shick HE; Garcia J; Deweese DM; Sun X; Stewart VJ; Macklin WB. 2004. The toppler mouse: A novel mutant exhibiting loss of Purkinje cells. J Comp Neurol 476(2):113-29. [PubMed: 15248193]  [MGI Ref ID J:91243]

Additional References

Cers1to related

Zhao L; Spassieva SD; Jucius TJ; Shultz LD; Shick HE; Macklin WB; Hannun YA; Obeid LM; Ackerman SL. 2011. A deficiency of ceramide biosynthesis causes cerebellar purkinje cell neurodegeneration and lipofuscin accumulation. PLoS Genet 7(5):e1002063. [PubMed: 21625621]  [MGI Ref ID J:172719]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhile maintaining a live colony, these mice are bred as heterozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   001800 FVB/NJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


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.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


(6.8)