Strain Name:

B6.129S2-En1tm1Alj/J

Stock Number:

003343

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Availability:

Cryopreserved - Ready for recovery

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; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Background Strain C57BL/6J
Donor Strain 129S2 via D3 ES cell line
GenerationN8pN1p (18-DEC-05)
Generation Definitions
 
Donating Investigator IMR Colony,   The Jackson Laboratory

Description
Mice homozygous for the En1tm1Alj targeted mutation die shortly after birth. They are missing the third and fourth cranial nerves as well as most of the colliculi and cerebellum. The brain phenotype can be less severe depending on the genetic background. There is also a disruption of the dorsal/ventral patterning of the limb paws, a disrupted sterum, and truncation of the 13th ribs. Deletion of mid-hindbrain tissue may be seen as early as embryonic day 9.5.

Control Information

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

Related Strains

Strains carrying   En1tm1Alj allele
002656   STOCK En1tm1Alj/J
View Strains carrying   En1tm1Alj     (1 strain)

Strains carrying other alleles of En1
002656   STOCK En1tm1Alj/J
007916   STOCK En1tm2(cre)Wrst/J
007912   STOCK En1tm2Alj/J
007917   STOCK En1tm7(cre/ESR1)Alj/J
007918   STOCK En1tm8.1Alj/J
View Strains carrying other alleles of En1     (5 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

En1tm1Alj/En1tm1Alj

        B6.129-En1tm1Alj
  • mortality/aging
  • partial postnatal lethality
    • born in normal numbers   (MGI Ref ID J:84363)
    • reduced vitality and frequently die before weaning   (MGI Ref ID J:84363)
  • growth/size phenotype
  • decreased body size
    • smaller than littermates within a few days of birth   (MGI Ref ID J:84363)
  • nervous system phenotype
  • abnormal cerebellar lobule formation
    • fusion of cerebellar lobules IV and V   (MGI Ref ID J:84363)
    • otherwise phenotypically normal cerebellum is seen as early as the third backcross generation to C57BL/6 and thereafter   (MGI Ref ID J:84363)
  • decreased inferior colliculus size
    • mild truncation seen in the midbrain in the area of the inferior colliculi   (MGI Ref ID J:84363)
  • limbs/digits/tail phenotype
  • abnormal autopod morphology
    • fur growth on the ventral surface of the forepaws   (MGI Ref ID J:84363)
    • abnormal digit morphology
      • circumferential nails on all digits   (MGI Ref ID J:84363)
      • polydactyly
        • 6th postaxial digit   (MGI Ref ID J:84363)
        • ectopic digits   (MGI Ref ID J:84363)
      • syndactyly   (MGI Ref ID J:84363)
  • integument phenotype
  • deformed nails
    • circumferential nails on all digits   (MGI Ref ID J:84363)

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

En1tm1Alj/En1tm1Alj

        involves: 129/Sv * C57BL/6J
  • limbs/digits/tail phenotype
  • abnormal apical ectodermal ridge morphology
    • ectopic expression ventrally of markers for the apical ectodermal ridge   (MGI Ref ID J:45301)
  • embryogenesis phenotype
  • abnormal apical ectodermal ridge morphology
    • ectopic expression ventrally of markers for the apical ectodermal ridge   (MGI Ref ID J:45301)

En1tm1Alj/En1tm1Alj

        either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)
  • mortality/aging
  • complete neonatal lethality
    • death usually within 24 hours of birth   (MGI Ref ID J:19212)
    • one mouse with a less severe phenotype survived to 7 days   (MGI Ref ID J:19212)
  • embryogenesis phenotype
  • abnormal apical ectodermal ridge morphology
    • thinner than in controls at E10.5   (MGI Ref ID J:34307)
  • limbs/digits/tail phenotype
  • abnormal limb morphology
    • in limbs examined, ventral tendons of digit flexor muscles are absent or poorly developed   (MGI Ref ID J:34307)
    • ventral skeletal elements such as falciform and sesamoid cartilages are absent or incompletely formed   (MGI Ref ID J:34307)
    • abnormal apical ectodermal ridge morphology
      • thinner than in controls at E10.5   (MGI Ref ID J:34307)
    • abnormal autopod morphology
      • dorsal transformation of ventral structures and ventral duplication of distal structures is observed in neonatal limbs   (MGI Ref ID J:34307)
      • paws display aspects of double dorsal paws   (MGI Ref ID J:34307)
      • abnormal digit morphology
        • outward splayed digits   (MGI Ref ID J:19212)
        • skin wrinkles on digits   (MGI Ref ID J:19212)
        • digits flex dorsally rather than ventrally   (MGI Ref ID J:34307)
        • ectopic digits
          • occasional ectopic ventral digits (digits 6, 7) are seen emanating from proximal paw pads in 10-15% of neonates   (MGI Ref ID J:34307)
        • polydactyly
          • 6th postaxial digit   (MGI Ref ID J:19212)
          • often with only one phalange   (MGI Ref ID J:19212)
          • usually involves only one forelimb   (MGI Ref ID J:19212)
          • one example of a preaxial supernumary digit on one paw (7 digits)   (MGI Ref ID J:19212)
        • syndactyly   (MGI Ref ID J:19212)
        • truncation of digits
          • mild truncation   (MGI Ref ID J:19212)
      • abnormal foot pad morphology
        • circumferential nails supplant distal, ventral foot pads; proximal metatarsal pads are present but possess few is any eccrine glands   (MGI Ref ID J:34307)
      • abnormal palmar eccrine gland morphology
        • ventrally restricted eccrine glands are largely absent   (MGI Ref ID J:34307)
  • skeleton phenotype
  • abnormal axial skeleton morphology   (MGI Ref ID J:19212)
    • decreased rib number
      • 13th rib pair missing or severely truncated in about 43% of animals   (MGI Ref ID J:19212)
    • short sternum
      • length reduced by 25%   (MGI Ref ID J:19212)
      • ossification centers reduced rostrally to caudally by 40-80%   (MGI Ref ID J:19212)
      • ossification centers asymmetric and abnormally fused in the midline   (MGI Ref ID J:19212)
      • fourth ossification center absent or rudimentary   (MGI Ref ID J:19212)
  • delayed bone ossification
    • delayed ossification of phalanges   (MGI Ref ID J:19212)
  • behavior/neurological phenotype
  • abnormal suckling behavior
    • pups fail to eat   (MGI Ref ID J:19212)
  • aphagia
    • most mice fail to eat   (MGI Ref ID J:19212)
    • only one, with a less severe phenotype actually ate   (MGI Ref ID J:19212)
  • nervous system phenotype
  • abnormal brain morphology   (MGI Ref ID J:19212)
    • abnormal brain development
      • abnormalities in the brain are apparent by E12.5, before primordia for the cerebellum and colliculi form   (MGI Ref ID J:19212)
      • abnormal midbrain development
        • reduced in size by E9.5   (MGI Ref ID J:19212)
        • abnormalities less obvious at E8.5   (MGI Ref ID J:19212)
    • abnormal cerebellum morphology
      • variable reduction in size   (MGI Ref ID J:19212)
      • absent cerebellum
        • in extreme examples, the cerebellum can be absent   (MGI Ref ID J:19212)
    • abnormal choroid plexus morphology
      • fused to the truncated colliculi   (MGI Ref ID J:19212)
    • decreased inferior colliculus size
      • truncated   (MGI Ref ID J:19212)
  • abnormal cranial nerve morphology   (MGI Ref ID J:19212)
    • absent oculomotor nerve
      • missing at E10.5 and E12.5   (MGI Ref ID J:19212)
    • absent trochlear nerve
      • missing at E10.5 and E12.5   (MGI Ref ID J:19212)
  • endocrine/exocrine gland phenotype
  • abnormal palmar eccrine gland morphology
    • ventrally restricted eccrine glands are largely absent   (MGI Ref ID J:34307)
  • integument phenotype
  • abnormal hair follicle dermal papilla morphology
    • present at base of epithelial structures in ventral and dorsal dermis   (MGI Ref ID J:34307)
  • abnormal hair follicle development
    • dorsally restricted follicles are seen along ventral as well as dorsal digit surfaces; ectopic ventral hairs on distal limbs   (MGI Ref ID J:34307)
  • abnormal nail morphology
    • in newborn mice, nails on digits 1-4 are circumferential in contrast to dorsally-positioned nails in wild-type neonates; nail plates are found on ventral and dorsal digit surfaces   (MGI Ref ID J:34307)
  • abnormal palmar eccrine gland morphology
    • ventrally restricted eccrine glands are largely absent   (MGI Ref ID J:34307)
  • wrinkled skin
    • skin wrinkles on digits   (MGI Ref ID J:19212)
View Research Applications

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

En1tm1Alj related

Developmental Biology Research
Limb Patterning Defects
Neurodevelopmental Defects

Neurobiology Research
Neurodevelopmental Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol En1tm1Alj
Allele Name targeted mutation 1, Alexandra L Joyner
Allele Type Targeted (knock-out)
Common Name(s) En-1hd;
Mutation Made By Alexandra Joyner,   Sloan-Kettering Institute
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name En1, engrailed 1
Chromosome 1
Gene Common Name(s) En-1; Mo-en.1; engrailed-1;
Molecular Note A neomycin selection cassette replaced 0.85 kb of exon 2, which encodes part of the homeobox domain. [MGI Ref ID J:19212]

Genotyping

Genotyping Information

Genotyping Protocols

En1tm1Alj, Standard PCR
NEOTD (Generic Neo), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Wurst W; Auerbach AB; Joyner AL. 1994. Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development 120(7):2065-75. [PubMed: 7925010]  [MGI Ref ID J:19212]

Additional References

Hanks M; Wurst W; Anson-Cartwright L; Auerbach AB; Joyner AL. 1995. Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2 [see comments] Science 269(5224):679-82. [PubMed: 7624797]  [MGI Ref ID J:27767]

Loomis CA; Harris E; Michaud J; Wurst W; Hanks M; Joyner AL. 1996. The mouse Engrailed-1 gene and ventral limb patterning. Nature 382(6589):360-3. [PubMed: 8684466]  [MGI Ref ID J:34307]

Loomis CA; Kimmel RA; Tong CX; Michaud J; Joyner AL. 1998. Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs. Development 125(6):1137-48. [PubMed: 9463360]  [MGI Ref ID J:46971]

Matise MP; Joyner AL. 1997. Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J Neurosci 17(20):7805-16. [PubMed: 9315901]  [MGI Ref ID J:43464]

En1tm1Alj related

Adamska M; MacDonald BT; Sarmast ZH; Oliver ER; Meisler MH. 2004. En1 and Wnt7a interact with Dkk1 during limb development in the mouse. Dev Biol 272(1):134-44. [PubMed: 15242796]  [MGI Ref ID J:92327]

Bilovocky NA; Romito-DiGiacomo RR; Murcia CL; Maricich SM; Herrup K. 2003. Factors in the genetic background suppress the engrailed-1 cerebellar phenotype. J Neurosci 23(12):5105-12. [PubMed: 12832534]  [MGI Ref ID J:84363]

Cheng Y; Sudarov A; Szulc KU; Sgaier SK; Stephen D; Turnbull DH; Joyner AL. 2010. The Engrailed homeobox genes determine the different foliation patterns in the vermis and hemispheres of the mammalian cerebellum. Development 137(3):519-29. [PubMed: 20081196]  [MGI Ref ID J:156169]

Cygan JA; Johnson RL; McMahon AP. 1997. Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutants. Development 124(24):5021-32. [PubMed: 9362463]  [MGI Ref ID J:45301]

Deckelbaum RA; Majithia A; Booker T; Henderson JE; Loomis CA. 2006. The homeoprotein engrailed 1 has pleiotropic functions in calvarial intramembranous bone formation and remodeling. Development 133(1):63-74. [PubMed: 16319118]  [MGI Ref ID J:104802]

Hanks M; Wurst W; Anson-Cartwright L; Auerbach AB; Joyner AL. 1995. Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2 [see comments] Science 269(5224):679-82. [PubMed: 7624797]  [MGI Ref ID J:27767]

Liu A; Joyner AL. 2001. EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development 128(2):181-91. [PubMed: 11124114]  [MGI Ref ID J:66592]

Loomis CA; Harris E; Michaud J; Wurst W; Hanks M; Joyner AL. 1996. The mouse Engrailed-1 gene and ventral limb patterning. Nature 382(6589):360-3. [PubMed: 8684466]  [MGI Ref ID J:34307]

Loomis CA; Kimmel RA; Tong CX; Michaud J; Joyner AL. 1998. Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs. Development 125(6):1137-48. [PubMed: 9463360]  [MGI Ref ID J:46971]

Louvi A; Alexandre P; Metin C; Wurst W; Wassef M. 2003. The isthmic neuroepithelium is essential for cerebellar midline fusion. Development 130(22):5319-30. [PubMed: 14507778]  [MGI Ref ID J:85727]

Matise MP; Joyner AL. 1997. Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J Neurosci 17(20):7805-16. [PubMed: 9315901]  [MGI Ref ID J:43464]

Moran JL; Shifley ET; Levorse JM; Mani S; Ostmann K; Perez-Balaguer A; Walker DM; Vogt TF; Cole SE. 2009. Manic fringe is not required for embryonic development, and fringe family members do not exhibit redundant functions in the axial skeleton, limb, or hindbrain. Dev Dyn 238(7):1803-1812. [PubMed: 19479951]  [MGI Ref ID J:149312]

Murcia CL; Bilovocky NA; Herrup K. 2004. Dissecting complex genetic interactions that influence the Engrailed-1 limb phenotype. Mamm Genome 15(5):352-60. [PubMed: 15170224]  [MGI Ref ID J:90096]

Murcia CL; Gulden FO; Cherosky NA; Herrup K. 2007. A genetic study of the suppressors of the Engrailed-1 cerebellar phenotype. Brain Res 1140:170-8. [PubMed: 16884697]  [MGI Ref ID J:120598]

Sillitoe RV; Stephen D; Lao Z; Joyner AL. 2008. Engrailed homeobox genes determine the organization of Purkinje cell sagittal stripe gene expression in the adult cerebellum. J Neurosci 28(47):12150-62. [PubMed: 19020009]  [MGI Ref ID J:142371]

Sillitoe RV; Vogel MW; Joyner AL. 2010. Engrailed homeobox genes regulate establishment of the cerebellar afferent circuit map. J Neurosci 30(30):10015-24. [PubMed: 20668186]  [MGI Ref ID J:162855]

Simon HH; Saueressig H; Wurst W; Goulding MD; O'Leary DD. 2001. Fate of midbrain dopaminergic neurons controlled by the engrailed genes. J Neurosci 21(9):3126-34. [PubMed: 11312297]  [MGI Ref ID J:68925]

Simon HH; Scholz C; O'Leary DD. 2005. Engrailed genes control developmental fate of serotonergic and noradrenergic neurons in mid- and hindbrain in a gene dose-dependent manner. Mol Cell Neurosci 28(1):96-105. [PubMed: 15607945]  [MGI Ref ID J:95392]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Purchasing information

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing
Order this mouse

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $1980.00
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 for further information.

Supply Notes

  • Cryorecovery - Standard.
    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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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
Order this mouse

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2574.00
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 for further information.

Supply Notes

  • Cryorecovery - Standard.
    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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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 for further information.

General Supply Notes

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

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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