Strain Name:

B6.Cg-Fig4plt1/MmJ

Stock Number:

017800

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The pale tremor (plt) allele is a spontaneous retrotransposon insertion in the Fig4 gene and is associated with Charcot-Marie-Tooth disease type 4J (CMT4J). Homozygous mice exhibit neuronal degeneration, juvenile lethality and diluted pigmentation.

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; Spontaneous Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation+pN1
Generation Definitions
 
Donating Investigator Miriam Meisler,   University of Michigan

Description
The pale tremor (plt) allele is a spontaneous retrotransposon insertion in the Fig4 gene. FIG4, a lipid phosphatase homolog of the yeast SAC (suppressor of actin), catalyzes removal of a phosphate from PI(3.5)P2, a membrane-bound phospholipid involved in the trafficking and fusion of intracellular vesicles. Mutations in human FIG4 are associated with Charcot-Marie-Tooth disease type 4J (CMT4J). Initially identified by tremors, an abnormal gait, which progresses to a loss of mobility, small size, juvenile lethality and diluted pigmentation, homozygous mice are characterized by spongiform degeneration of the brain and loss of neurons from peripheral ganglia. Neuron loss and accumulation of cytoplasmic vacuoles is observed in layers 4 and 5 of the cortex, deep cerebellar nuclei, and dorsal root ganglia. Homozygote survival is dependent on strain background. On the C57BL/6 background, homozygotes are neonatal lethal; on a C3H background homozygotes survive to two weeks; on a mixed C57BL/6 and C3HeB/FeJ background, homozygotes survive 4-6 weeks. These mice may be useful in studies of Charcot-Marie-Tooth disease type 4J.

Development
The pale tremor plt mutation arose spontaneously on a mixed strain background that included C57BL/6J, C3H, 129P2/Ola and SJL in the laboratory of Dr. Miriam Meisler at the University of Michigan. Mice carrying the mutation have been crossed for at least 21 generations to C57BL/6J. Pale tremor is a 5.5 kB ETn2b retrotransposon insertion in the FIG4 homolog Fig4 gene. The retrotransposon is inserted 384 bp upstream of exon 19 and results in abnormal splicing from exon 18. Low levels of transcript cannot be detected by Northern blot, but can be detected by RT-PCR. Functionally, plt is a null mutation. The strain is maintained as a cross to C57BL/6. Upon arrival, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Fig4plt1 allele
017801   C3Fe.Cg-Fig4plt1/MmJ
View Strains carrying   Fig4plt1     (1 strain)

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).
Charcot-Marie-Tooth Disease, Type 4j; CMT4J
Yunis-Varon Syndrome; YVS
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Amyotrophic Lateral Sclerosis 11; ALS11   (FIG4)
Polymicrogyria, Bilateral Temporooccipital; BTOP   (FIG4)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Fig4plt1/Fig4plt1

        B6.Cg-Fig4plt1
  • cardiovascular system phenotype
  • abnormal heart atrium morphology
    • significant degeneration of the atria with large, transparent vacuoles   (MGI Ref ID J:190368)

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

Fig4plt1/Fig4plt1

        involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL
  • mortality/aging
  • premature death
    • all mice die by 6 weeks   (MGI Ref ID J:122737)
    • juvenile lethality at 6-8 weeks of age   (MGI Ref ID J:185989)
  • behavior/neurological phenotype
  • abnormal motor capabilities/coordination/movement
    • severe movement disorder by 30 days of age   (MGI Ref ID J:185989)
    • abnormal gait
      • mice have a 'swimming' gait   (MGI Ref ID J:122737)
    • abnormal limb posture
    • impaired coordination
      • progressive loss of mobility   (MGI Ref ID J:122737)
    • tremors   (MGI Ref ID J:122737)
      • by 30 days of age   (MGI Ref ID J:185989)
  • nervous system phenotype
  • abnormal action potential
    • sciatic nerves have reduced amplitude of compound muscle action potential   (MGI Ref ID J:122737)
  • abnormal nerve conduction
    • sciatic nerve conduction velocity is slowed   (MGI Ref ID J:122737)
    • sciatic nerve conduction velocity reduced to 50% of velocity in control mice   (MGI Ref ID J:185989)
  • abnormal nervous system morphology   (MGI Ref ID J:185989)
    • abnormal motor neuron morphology
      • at 6 weeks, spinal motor neurons accumulates vacuoles prior to cell loss   (MGI Ref ID J:122737)
    • abnormal sciatic nerve morphology
      • mice exhibit fewer large-diameter myelinated axons   (MGI Ref ID J:122737)
      • sciatic nerve conduction velocity is slowed   (MGI Ref ID J:122737)
      • sciatic nerves have reduced amplitude of compound muscle action potential   (MGI Ref ID J:122737)
    • astrocytosis   (MGI Ref ID J:185989)
    • neuron degeneration
      • visible at week 1, mice exhibit neonatal degeneration in sensory and autonomic ganglia with loss of neurons in from layers 4 and 5 of the cortex, deep cerebellar nuclei, thalamus, pons and medulla   (MGI Ref ID J:122737)
    • spongiform encephalopathy
      • in deep layers of cortex, cerebellar nuclei, hippocampus, brainstem, and dorsal root ganglia   (MGI Ref ID J:185989)
  • demyelination
    • reduced sciatic nerve myelination   (MGI Ref ID J:185989)
    • low abundance of myelin basic protein   (MGI Ref ID J:185989)
  • muscle phenotype
  • muscle weakness   (MGI Ref ID J:122737)
  • growth/size/body phenotype
  • decreased body size
    • decreased body weight   (MGI Ref ID J:122737)
  • hematopoietic system phenotype
  • spleen hypoplasia
    • severe tremors develop 2 weeks after birth   (MGI Ref ID J:122737)
  • immune system phenotype
  • spleen hypoplasia
    • severe tremors develop 2 weeks after birth   (MGI Ref ID J:122737)
  • pigmentation phenotype
  • abnormal melanosome morphology
    • clumps of melanosomes are visible in the few remaining pigmented hair follicles   (MGI Ref ID J:122737)
  • diluted coat color   (MGI Ref ID J:185989)
  • integument phenotype
  • abnormal hair follicle morphology
    • clumps of melanosomes are visible in the few remaining pigmented hair follicles   (MGI Ref ID J:122737)
    • decreased hair follicle number
      • pigment containing hair follicles are decreased in number   (MGI Ref ID J:122737)
  • diluted coat color   (MGI Ref ID J:185989)

Fig4plt1/Fig4plt1

        involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL
  • mortality/aging
  • premature death
    • survive to 1 -2 months of age   (MGI Ref ID J:173446)
  • nervous system phenotype
  • abnormal brain morphology
    • extensive autophagic inclusion bodies   (MGI Ref ID J:173446)
  • abnormal myelin sheath morphology
    • thinning of the myelin sheath of the sciatic nerve   (MGI Ref ID J:173446)
  • abnormal sciatic nerve morphology
    • thinning of the myelin sheath of the sciatic nerve   (MGI Ref ID J:173446)
  • astrocytosis   (MGI Ref ID J:173446)
  • decreased nerve conduction velocity
    • in the sciatic nerve   (MGI Ref ID J:173446)
  • neurodegeneration
    • severe spongiform degeneration in the brain and extensive loss of neurons from the peripheral ganglia   (MGI Ref ID J:173446)
    • neuron degeneration
      • extensive loss of neurons from peripheral ganglia   (MGI Ref ID J:173446)
      • neurons in layers 4 and 5 of the cortex, the deep cerebellar nuclei, and the dorsal root ganglia are severely affected with accumulation of vacuoles that fill the cytoplasm   (MGI Ref ID J:173446)
    • spongiform encephalopathy   (MGI Ref ID J:173446)
  • pigmentation phenotype
  • diluted coat color   (MGI Ref ID J:173446)
  • hypopigmentation   (MGI Ref ID J:173446)
  • integument phenotype
  • diluted coat color   (MGI Ref ID J:173446)

Fig4plt1/Fig4plt1

        involves: 129P2/OlaHsd * C3H * SJL
  • growth/size/body phenotype
  • abnormal incisor morphology
    • relative overgrowth of incisors   (MGI Ref ID J:203638)
  • decreased body weight   (MGI Ref ID J:203638)
  • postnatal growth retardation
    • impaired growth; skeleton is normal at birth but is smaller at P21   (MGI Ref ID J:203638)
  • craniofacial phenotype
  • abnormal craniofacial morphology
    • craniofacial morphology is altered   (MGI Ref ID J:203638)
    • abnormal incisor morphology
      • relative overgrowth of incisors   (MGI Ref ID J:203638)
  • hematopoietic system phenotype
  • abnormal bone marrow cell morphology/development
    • extensive vacuolization is seen in cultures of bone marrow mesenchymal stroma   (MGI Ref ID J:203638)
  • skeleton phenotype
  • abnormal bone ossification   (MGI Ref ID J:203638)
  • abnormal skeleton morphology
    • skeleton is normal at birth but is smaller at P21   (MGI Ref ID J:203638)
    • abnormal bone structure
      • bone volume fraction, bone surface, trabecular number and connectivity density are reduced to less than 50% of wild-type values   (MGI Ref ID J:203638)
      • abnormal compact bone morphology
        • lower cortical density of bones   (MGI Ref ID J:203638)
        • decreased compact bone thickness
          • femoral cortical thickness is reduced to less than 50% of wild-type values   (MGI Ref ID J:203638)
      • abnormal osteoblast morphology
        • extensive vacuolization is seen in cultures of isolated osteoblasts from calvarial tissue   (MGI Ref ID J:203638)
      • abnormal trabecular bone morphology
        • lower trabecular density of bones and reduction in size and density of trabeculae in vertebrae   (MGI Ref ID J:203638)
        • trabecular separation is increased more than 3-fold   (MGI Ref ID J:203638)
        • decreased bone trabecula number   (MGI Ref ID J:203638)
        • decreased trabecular bone connectivity density   (MGI Ref ID J:203638)
        • decreased trabecular bone volume   (MGI Ref ID J:203638)
      • decreased bone volume   (MGI Ref ID J:203638)
        • decreased trabecular bone volume   (MGI Ref ID J:203638)
    • decreased length of long bones
      • long bones are 20-25% smaller at P21 than in wild-type   (MGI Ref ID J:203638)
    • small clavicle
      • clavicles are 20-25% smaller at P21 than in wild-type, however their shape is normal   (MGI Ref ID J:203638)
      • however, pelvic bone shape is normal in newborns and at P21   (MGI Ref ID J:203638)
  • limbs/digits/tail phenotype
  • *normal* limbs/digits/tail phenotype
    • mice do not exhibit aplasia or hypoplasia of digits on the front or rear limb   (MGI Ref ID J:203638)
View Research Applications

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

Neurobiology Research
Ataxia (Movement) Defects
Neurodegeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Fig4plt1
Allele Name pale tremor
Allele Type Spontaneous
Common Name(s) Fig4paletremor; plt;
Mutation Made By Miriam Meisler,   University of Michigan
Strain of Originmixed
Gene Symbol and Name Fig4, FIG4 homolog (S. cerevisiae)
Chromosome 10
Gene Common Name(s) A530089I17Rik; AI326867; ALS11; BTOP; CMT4J; KIAA0274; RGD1311375; RIKEN cDNA A530089I17 gene; SAC3; YVS; dJ249I4.1; expressed sequence AI326867;
Molecular Note The mouse retrotransposon ETn2Beta was inserted 384 bp upstream of exon 19 in the same orientation as the gene and was flanked by a duplication of the hexanucleotide CCCCTG. Northern blot did not detect transcript from mutants using a cDNA probe containing exons 8-15. [MGI Ref ID J:122737]

Genotyping

Genotyping Information

Genotyping Protocols

Fig4plt1, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Chow CY; Zhang Y; Dowling JJ; Jin N; Adamska M; Shiga K; Szigeti K; Shy ME; Li J; Zhang X; Lupski JR; Weisman LS; Meisler MH. 2007. Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J. Nature 448(7149):68-72. [PubMed: 17572665]  [MGI Ref ID J:122737]

Additional References

Fig4plt1 related

Campeau PM; Lenk GM; Lu JT; Bae Y; Burrage L; Turnpenny P; Roman Corona-Rivera J; Morandi L; Mora M; Reutter H; Vulto-van Silfhout AT; Faivre L; Haan E; Gibbs RA; Meisler MH; Lee BH. 2013. Yunis-Varon syndrome is caused by mutations in FIG4, encoding a phosphoinositide phosphatase. Am J Hum Genet 92(5):781-91. [PubMed: 23623387]  [MGI Ref ID J:203638]

Ferguson CJ; Lenk GM; Jones JM; Grant AE; Winters JJ; Dowling JJ; Giger RJ; Meisler MH. 2012. Neuronal expression of Fig4 is both necessary and sufficient to prevent spongiform neurodegeneration. Hum Mol Genet 21(16):3525-34. [PubMed: 22581779]  [MGI Ref ID J:185989]

Ferguson CJ; Lenk GM; Meisler MH. 2009. Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2. Hum Mol Genet 18(24):4868-4878. [PubMed: 19793721]  [MGI Ref ID J:154296]

Katona I; Zhang X; Bai Y; Shy ME; Guo J; Yan Q; Hatfield J; Kupsky WJ; Li J. 2011. Distinct pathogenic processes between Fig4-deficient motor and sensory neurons. Eur J Neurosci 33(8):1401-10. [PubMed: 21410794]  [MGI Ref ID J:177325]

Lenk GM; Ferguson CJ; Chow CY; Jin N; Jones JM; Grant AE; Zolov SN; Winters JJ; Giger RJ; Dowling JJ; Weisman LS; Meisler MH. 2011. Pathogenic Mechanism of the FIG4 Mutation Responsible for Charcot-Marie-Tooth Disease CMT4J. PLoS Genet 7(6):e1002104. [PubMed: 21655088]  [MGI Ref ID J:173446]

Porrello E; Rivellini C; Dina G; Triolo D; Del Carro U; Ungaro D; Panattoni M; Feltri ML; Wrabetz L; Pardi R; Quattrini A; Previtali SC. 2014. Jab1 regulates Schwann cell proliferation and axonal sorting through p27. J Exp Med 211(1):29-43. [PubMed: 24344238]  [MGI Ref ID J:208363]

Reifler A; Lenk GM; Li X; Groom L; Brooks SV; Wilson D; Bowerson M; Dirksen RT; Meisler MH; Dowling JJ. 2013. Murine Fig4 is dispensable for muscle development but required for muscle function. Skelet Muscle 3(1):21. [PubMed: 24004519]  [MGI Ref ID J:202033]

Winters JJ; Ferguson CJ; Lenk GM; Giger-Mateeva VI; Shrager P; Meisler MH; Giger RJ. 2011. Congenital CNS Hypomyelination in the Fig4 Null Mouse Is Rescued by Neuronal Expression of the PI(3,5)P2 Phosphatase Fig4. J Neurosci 31(48):17736-51. [PubMed: 22131434]  [MGI Ref ID J:178138]

Zhang Y; McCartney AJ; Zolov SN; Ferguson CJ; Meisler MH; Sutton MA; Weisman LS. 2012. Modulation of synaptic function by VAC14, a protein that regulates the phosphoinositides PI(3,5)P(2) and PI(5)P. EMBO J 31(16):3442-56. [PubMed: 22842785]  [MGI Ref ID J:188700]

Zolov SN; Bridges D; Zhang Y; Lee WW; Riehle E; Verma R; Lenk GM; Converso-Baran K; Weide T; Albin RL; Saltiel AR; Meisler MH; Russell MW; Weisman LS. 2012. In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P. Proc Natl Acad Sci U S A 109(43):17472-7. [PubMed: 23047693]  [MGI Ref ID J:190368]

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. Homozygote survival is dependent on strain background. On the C57BL/6 background, homozygotes are neonatal lethal; on a C3H background homozygotes survive to two weeks; on a mixed background, homozygotes survive 4-6 weeks.

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
   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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