Strain Name:

B6.129(C)-Nrp1tm1Ddg/J

Stock Number:

005245

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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
Generation?+N1p (08-MAY-05)
Generation Definitions
 
Donating Investigator David D. Ginty,   Johns Hopkins University

Description
Mice that are homozygous for the targeted mutation are viable, but experience fertility problems. Homozygous mice have increased incidence of postnatal lethality by 7 days of age. Mutant mice express normal levels of gene product of the variant protein that does not bind semaphorins and retains binding ability for VEGF. Homozygotes display axon guidance defects with little or no binding activity of semaphorin 3A or 3C to axons in the dorsal root entry zone. Cultured neurons isolated from mutant mice do not respond to semaphorin3A. Cranial and spinal neurons from E11.5 and E12.5 embryos are disorganized, defasciculated and have abnormal errant projections. This mutant mouse strain may be useful in studies of neural development and axonal guidance.

Development
A targeting vector containing loxP site flanked selection cassette (neomycin resistance and herpes simplex virus thymidine kinase genes) and sequence encoding a 7 amino acid substitution in exon 2 was utilized in the construction of this mutant. The construct was electroporated into 129.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to mice expressing Cre recombinase (BALB/c-Tg(CMV-cre)1Cgn/J Stock#3465), and then backcrossed to C57BL/6 for 6 generations

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Nrp1
005247   B6.129(SJL)-Nrp1tm2Ddg/J
View Strains carrying other alleles of Nrp1     (1 strain)

Phenotype

Phenotype Information

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.

Nrp1tm1Ddg/Nrp1tm1Ddg

        involves: 129P2/OlaHsd * C57BL/6
  • mortality/aging
  • postnatal lethality
    • 40% die by P7   (MGI Ref ID J:93799)
  • cardiovascular system phenotype
  • dilated heart atrium
    • exhibited bilateral atrial enlargement, however no vascular branching defects were observed   (MGI Ref ID J:93799)
  • growth/size/body phenotype
  • postnatal growth retardation
    • 70% of P7 survivors are growth retarded   (MGI Ref ID J:93799)
  • nervous system phenotype
  • abnormal axon guidance
    • guidance of ophthalmic nerve axons and cutaneous sensory neurons was abnormal so that projections extended beyond their normal zones   (MGI Ref ID J:93799)
  • abnormal corpus callosum morphology
    • callosal axons displayed varying degrees of defasciculation with agenesis of corpus callosum resulting in the formation of Probst bundles in extreme cases   (MGI Ref ID J:93799)
  • abnormal cranial nerve morphology   (MGI Ref ID J:93799)
    • abnormal trigeminal nerve morphology
      • defasciculated and abnormally extended ophthalmic branch of the trigeminal nerve, however defects were less severe than in Nrp1   (MGI Ref ID J:93799)
    • abnormal vestibulocochlear nerve morphology
      • E12.5 mutants have additional smaller fiber bundles that extend beyond their normal termination zones within the sensory end organs with projection defects persisting at E14.5 and E15.5   (MGI Ref ID J:93799)
  • abnormal dorsal root ganglion morphology
    • many cutaneous afferent axons entered the gray matter a E14.5 with some projections extending into the most ventral regions of the spinal cord   (MGI Ref ID J:93799)
    • at P2, some axons were outside their normal termination zones, along the midline and in the medial-ventral spinal cord   (MGI Ref ID J:93799)
  • abnormal hippocampus morphology
    • entorhinohippocampal axons were no longer restricted in the stratum lacunosum-moleculare of the ipsilateral hippocampus with many fibers innervating ectopic layers   (MGI Ref ID J:93799)
  • abnormal spinal nerve morphology
    • disorganized peripheral projections of spinal nerves in E11.5 mutants   (MGI Ref ID J:93799)
  • cellular phenotype
  • abnormal axon guidance
    • guidance of ophthalmic nerve axons and cutaneous sensory neurons was abnormal so that projections extended beyond their normal zones   (MGI Ref ID J:93799)

Nrp1tm1Ddg/Nrp1tm1Ddg

        involves: 129P2/OlaHsd
  • immune system phenotype
  • abnormal T cell physiology
    • defective T-cell priming by antigen   (MGI Ref ID J:161856)
  • abnormal dendritic cell physiology
    • impaired dendritic cell migration   (MGI Ref ID J:161856)
  • vision/eye phenotype
  • *normal* vision/eye phenotype
    • mice exhibit normal retinal stratification   (MGI Ref ID J:172268)
  • hematopoietic system phenotype
  • abnormal T cell physiology
    • defective T-cell priming by antigen   (MGI Ref ID J:161856)
View Research Applications

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

Nrp1tm1Ddg related

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Neurodevelopmental Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Nrp1tm1Ddg
Allele Name targeted mutation 1, David D Ginty
Allele Type Targeted (knock-in)
Common Name(s) npn-1Sema-;
Mutation Made By Dori (Dorothy) Reimert,   Johns Hopkins University
Strain of Origin129P2/OlaHsd
ES Cell Line NameGK129
ES Cell Line Strain129P2/OlaHsd
Promoter Nrp1, neuropilin 1, mouse, laboratory
Molecular Note Exon 2 was replaced with a mutated exon 2 encoding a 7 amino acid substitution in three regions of the amino-terminal CUB domain and a Pgk-neo cassette flanked by loxP sites was inserted within the intron upstream of exon 2. The Pgk-neo cassette was removed by mating with mice expressing germline Cre-recombinase. Mutation of this site was shown to abolish Sema3 family binding but not VEGF binding. Immunohistochemistry showed that homozygotes express normal levels of protein. [MGI Ref ID J:93799]

Genotyping

Genotyping Information

Genotyping Protocols

Nrp1tm1Ddg, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Gu C; Rodriguez ER; Reimert DV; Shu T; Fritzsch B; Richards LJ; Kolodkin AL; Ginty DD. 2003. Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev Cell 5(1):45-57. [PubMed: 12852851]  [MGI Ref ID J:93799]

Additional References

Nrp1tm1Ddg related

Cariboni A; Davidson K; Rakic S; Maggi R; Parnavelas JG; Ruhrberg C. 2011. Defective gonadotropin-releasing hormone neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2: implications for the aetiology of hypogonadotropic hypogonadism. Hum Mol Genet 20(2):336-44. [PubMed: 21059704]  [MGI Ref ID J:166892]

Cioni JM; Telley L; Saywell V; Cadilhac C; Jourdan C; Huber AB; Huang JZ; Jahannault-Talignani C; Ango F. 2013. SEMA3A signaling controls layer-specific interneuron branching in the cerebellum. Curr Biol 23(10):850-61. [PubMed: 23602477]  [MGI Ref ID J:199730]

Erskine L; Reijntjes S; Pratt T; Denti L; Schwarz Q; Vieira JM; Alakakone B; Shewan D; Ruhrberg C. 2011. VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm. Neuron 70(5):951-65. [PubMed: 21658587]  [MGI Ref ID J:174966]

Faulkner RL; Low LK; Liu XB; Coble J; Jones EG; Cheng HJ. 2008. Dorsal turning of motor corticospinal axons at the pyramidal decussation requires plexin signaling. Neural Dev 3:21. [PubMed: 18727829]  [MGI Ref ID J:160739]

Gu C; Yoshida Y; Livet J; Reimert DV; Mann F; Merte J; Henderson CE; Jessell TM; Kolodkin AL; Ginty DD. 2005. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science 307(5707):265-8. [PubMed: 15550623]  [MGI Ref ID J:95697]

Haupt C; Kloos K; Faus-Kessler T; Huber AB. 2010. Semaphorin 3A-Neuropilin-1 signaling regulates peripheral axon fasciculation and pathfinding but not developmental cell death patterns. Eur J Neurosci 31(7):1164-72. [PubMed: 20345923]  [MGI Ref ID J:160945]

Hayashi M; Nakashima T; Taniguchi M; Kodama T; Kumanogoh A; Takayanagi H. 2012. Osteoprotection by semaphorin 3A. Nature 485(7396):69-74. [PubMed: 22522930]  [MGI Ref ID J:183995]

Huber AB; Kania A; Tran TS; Gu C; De Marco Garcia N; Lieberam I; Johnson D; Jessell TM; Ginty DD; Kolodkin AL. 2005. Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. Neuron 48(6):949-64. [PubMed: 16364899]  [MGI Ref ID J:107594]

Huettl RE; Huber AB. 2011. Cranial nerve fasciculation and Schwann cell migration are impaired after loss of Npn-1. Dev Biol 359(2):230-41. [PubMed: 21925156]  [MGI Ref ID J:178497]

Joza S; Wang J; Fox E; Hillman V; Ackerley C; Post M. 2012. Loss of semaphorin-neuropilin-1 signaling causes dysmorphic vascularization reminiscent of alveolar capillary dysplasia. Am J Pathol 181(6):2003-17. [PubMed: 23063659]  [MGI Ref ID J:190719]

Matsuoka RL; Jiang Z; Samuels IS; Nguyen-Ba-Charvet KT; Sun LO; Peachey NS; Chedotal A; Yau KW; Kolodkin AL. 2012. Guidance-cue control of horizontal cell morphology, lamination, and synapse formation in the mammalian outer retina. J Neurosci 32(20):6859-68. [PubMed: 22593055]  [MGI Ref ID J:184894]

Matsuoka RL; Nguyen-Ba-Charvet KT; Parray A; Badea TC; Chedotal A; Kolodkin AL. 2011. Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina. Nature 470(7333):259-63. [PubMed: 21270798]  [MGI Ref ID J:172268]

McKenna CC; Munjaal RP; Lwigale PY. 2012. Distinct roles for neuropilin1 and neuropilin2 during mouse corneal innervation. PLoS One 7(5):e37175. [PubMed: 22615927]  [MGI Ref ID J:187230]

Roffers-Agarwal J; Gammill LS. 2009. Neuropilin receptors guide distinct phases of sensory and motor neuronal segmentation. Development 136(11):1879-88. [PubMed: 19403658]  [MGI Ref ID J:149562]

Schwarz Q; Gu C; Fujisawa H; Sabelko K; Gertsenstein M; Nagy A; Taniguchi M; Kolodkin AL; Ginty DD; Shima DT; Ruhrberg C. 2004. Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve. Genes Dev 18(22):2822-34. [PubMed: 15545635]  [MGI Ref ID J:94050]

Schwarz Q; Vieira JM; Howard B; Eickholt BJ; Ruhrberg C. 2008. Neuropilin 1 and 2 control cranial gangliogenesis and axon guidance through neural crest cells. Development 135(9):1605-13. [PubMed: 18356247]  [MGI Ref ID J:134486]

Sun LO; Jiang Z; Rivlin-Etzion M; Hand R; Brady CM; Matsuoka RL; Yau KW; Feller MB; Kolodkin AL. 2013. On and off retinal circuit assembly by divergent molecular mechanisms. Science 342(6158):1241974. [PubMed: 24179230]  [MGI Ref ID J:202884]

Takamatsu H; Takegahara N; Nakagawa Y; Tomura M; Taniguchi M; Friedel RH; Rayburn H; Tessier-Lavigne M; Yoshida Y; Okuno T; Mizui M; Kang S; Nojima S; Tsujimura T; Nakatsuji Y; Katayama I; Toyofuku T; Kikutani H; Kumanogoh A. 2010. Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Nat Immunol 11(7):594-600. [PubMed: 20512151]  [MGI Ref ID J:161856]

Vieira JM; Schwarz Q; Ruhrberg C. 2007. Selective requirements for NRP1 ligands during neurovascular patterning. Development 134(10):1833-43. [PubMed: 17428830]  [MGI Ref ID J:121420]

Yamamoto M; Suzuki K; Okuno T; Ogata T; Takegahara N; Takamatsu H; Mizui M; Taniguchi M; Chedotal A; Suto F; Fujisawa H; Kumanogoh A; Kikutani H. 2008. Plexin-A4 negatively regulates T lymphocyte responses. Int Immunol 20(3):413-20. [PubMed: 18209113]  [MGI Ref ID J:131739]

de Anda FC; Rosario AL; Durak O; Tran T; Graff J; Meletis K; Rei D; Soda T; Madabhushi R; Ginty DD; Kolodkin AL; Tsai LH. 2012. Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex. Nat Neurosci 15(7):1022-31. [PubMed: 22683681]  [MGI Ref ID J:191610]

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 & HusbandryThis strain is maintained as a heterozygote. Homozygotes are viable but experience fertility problems.

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* $2450.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $1600.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 11 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* $3185.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $2080.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 11 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
 
  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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