Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129S4 via J1 ES cell line   Donating Investigator The Jackson Laboratory,

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Ntf3^tm1Jae targeted mutation are smaller than their normal littermates and most die shortly after birth. Survivors die prior to weaning. They display limb ataxia, an inability to position the limbs properly when attempting to move, and there is a tendency for all four limbs to intermittently stiffen in an extensor posture. Autopsy showed all peripheral ganglia markedly smaller in the mutant. Spinal proprioceptive afferents and their peripheral sense organs are completely absent. Heterozygous mice appear normal; however, the number of muscle spindles in heterozygotes is half that of normal wildtype siblings. There is approximately a 50% reduction in the sympathetic superior cervical ganglion (SCG) neurons caused by excessive apoptosis of sympathetic neuroblasts during neurogenesis.

Control Information

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

Related Strains

Strains carrying   Ntf3^tm1Jae allele

002276

STOCK Ntf3tm1Jae/J

View Strains carrying   Ntf3^tm1Jae     (1 strain)

Strains carrying other alleles of Ntf3

003541

B6.129S4-Ntf3tm2Jae/J

View Strains carrying other alleles of Ntf3     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ntf3^tm1Jae/Ntf3^tm1Jae

        involves: 129S4/SvJae * C57BL/6J

• nervous system phenotype
• abnormal muscle innervation (MGI Ref ID J:90280)
  • on P1 the fungiform papillae of the tongue are partially denervated
• abnormal sensory neuron innervation (MGI Ref ID J:90280)
  • innervation of the somatosensory prominences is virtually absent

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

Ntf3^tm1Jae/Ntf3⁺

        involves: 129S4/SvJae * BALB/c

• nervous system phenotype
• abnormal dorsal root ganglion morphology (MGI Ref ID J:53825)
  • mice exhibit a loss of myelinated fibers in the dorsal root ganglion
• abnormal stellate ganglion morphology (MGI Ref ID J:62748)
  • fewer stellate ganglion neurons at P0 and P60 than in wild-type
• decreased sensory neuron number (MGI Ref ID J:53825)
  • mice exhibit a 17% loss in sensory neurons in the dorsal root ganglion
• cardiovascular system phenotype
• abnormal cardiovascular system physiology (MGI Ref ID J:62748)
  • adults exhibit lower sympathetic tonus than wild-type
• decreased heart rate (MGI Ref ID J:62748)
  • adults exhibit lower resting heart rates than wild-type
• homeostasis/metabolism phenotype
• abnormal noradrenaline level (MGI Ref ID J:62748)
  • 37% decrease in adult heart ventricular norepinephrine concentrations, however no differences seen at birth
• muscle phenotype
• abnormal muscle morphology (MGI Ref ID J:23882)
  • 50% reduction of muscle spindles
  • muscles exhibit fewer myelinated fibers than in wild-type mice (52+/-4 compared to 76+/-2 in wild-type mice)

Ntf3^tm1Jae/Ntf3^tm1Jae

        involves: 129S4/SvJae * BALB/c

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:23882)
  • by 3 weeks of age
• behavior/neurological phenotype
• abnormal sensory capabilities/reflexes/nociception (MGI Ref ID J:23882)
  • exhibit a tendency of all four limbs to intermittently stiffen in an extensor posture
• ataxia (MGI Ref ID J:23882)
  • limb ataxia
• impaired limb coordination (MGI Ref ID J:23882)
  • display an inability to position the extremities properly when attempting to move
• growth/size phenotype
• decreased body size (MGI Ref ID J:23882)
  • retardation
• decreased body weight (MGI Ref ID J:62748)
  • weigh 20% less than controls at birth
• muscle phenotype
• abnormal muscle morphology (MGI Ref ID J:23882)
• absent golgi tendon organ (MGI Ref ID J:23882)
• absent muscle spindles (MGI Ref ID J:23882)
  • absent muscle spindles
• nervous system phenotype
• abnormal dorsal root ganglion morphology (MGI Ref ID J:23882)
  • loss of carbonic anhydrase (CA) positive neurons, which are mostly L4 dorsal root ganglion neurons
• abnormal proprioceptive neuron morphology (MGI Ref ID J:23882)
  • central branch of the proprioceptive Ia fibers innvervating spinal cord layer IX is absent
• small dorsal root ganglion (MGI Ref ID J:23882)
• abnormal muscle innervation (MGI Ref ID J:23882)
  • show no evidence of afferent nerve fiber-muscle contacts
• abnormal stellate ganglion morphology (MGI Ref ID J:62748)
  • fewer stellate ganglion neurons at P0 and P60 than in heterozygotes or wild-type
• absent golgi tendon organ (MGI Ref ID J:23882)
• absent muscle spindles (MGI Ref ID J:23882)
  • absent muscle spindles
• small mesencephalic trigeminal nucleus (MGI Ref ID J:23882)
• small nodose ganglion (MGI Ref ID J:23882)
• small superior cervical ganglion (MGI Ref ID J:23882)
• small trigeminal ganglion (MGI Ref ID J:23882)

Ntf3^tm1Jae/Ntf3^tm1Jae

        involves: 129S4/SvJae

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:43444)
  • mutants die soon after birth from cardiac defects
• nervous system phenotype
• abnormal dorsal root ganglion morphology (MGI Ref ID J:43444)
  • a 63% decrease compared to wild-type in the overall number of dorsal root ganglia neurons at L4 is seen in newborn mice
• absent proprioceptive neurons (MGI Ref ID J:43444)
  • essentially no proprioceptive neurons are present
• absent muscle spindles (MGI Ref ID J:43444)
  • no spindle bundles are seen
• muscle phenotype
• absent muscle spindles (MGI Ref ID J:43444)
  • no spindle bundles are seen

Ntf3^tm1Jae/Ntf3^tm1Jae

        involves: 129S4/SvJae * C57BL/6

• nervous system phenotype
• abnormal dorsal root ganglion morphology (MGI Ref ID J:83461)
  • 70% of dorsal root ganglia neurons are lost relative to in wild-type mice
• absent proprioceptive neurons (MGI Ref ID J:83461)
  • proprioceptive neurons are lost
• absent muscle spindles (MGI Ref ID J:83461)
  • no muscle spindles are found in the soleus muscle during development and at later stages
• muscle phenotype
• absent muscle spindles (MGI Ref ID J:83461)
  • no muscle spindles are found in the soleus muscle during development and at later stages

View Research Applications

Research Applications

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

Ntf3^tm1Jae related

Apoptosis Research
Extracellular Modulators

Cancer Research
Genes Regulating Growth and Proliferation
Growth Factors/Receptors/Cytokines

Developmental Biology Research
Mesodermal Defects (Myogenesis Defects)

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines
Inflammation

Neurobiology Research
Ataxia (Movement) Defects
Neurotrophic Factor Defects
Vestibular and Hearing Defects

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ntf3tm1Jae
Allele Name		targeted mutation 1, Rudolf Jaenisch
Allele Type		Targeted (knock-out)
Common Name(s)		NT-3-; NT3-;
Mutation Made By		Rudolf Jaenisch,   Massachusetts Institute of Technology
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Ntf3, neurotrophin 3
Chromosome		6
Gene Common Name(s)		AI316846; AI835689; EST AI316846; HDNF; MGC129711; NGF-2; NGF2; NT-3; NT3; Ntf-3; expressed sequence AI835689;
Molecular Note		The entire coding region for the Ntf3 gene was replaced by a neomycin cassette. [MGI Ref ID J:23882]

Genotyping

Genotyping Information

Genotyping Protocols

NEOTD (Generic Neo), STD PCR, vers. 1
Ntf3^tm1Jae, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Ernfors P; Lee KF; Kucera J; Jaenisch R. 1994. Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77(4):503-12. [PubMed: 7514502]  [MGI Ref ID J:23882]

Additional References

ElShamy WM; Linnarsson S; Lee KF; Jaenisch R; Ernfors P. 1996. Prenatal and postnatal requirements of NT-3 for sympathetic neuroblast survival and innervation of specific targets. Development 122(2):491-500. [PubMed: 8625800]  [MGI Ref ID J:69121]

Fan L; Girnius S; Oakley B. 2004. Support of trigeminal sensory neurons by nonneuronal p75 neurotrophin receptors. Brain Res Dev Brain Res 150(1):23-39. [PubMed: 15126035]  [MGI Ref ID J:90280]

Kucera J; Fan G; Walro J; Copray S; Tessarollo L; Jaenisch R. 1998. Neurotrophin-3 and trkC in muscle are non-essential for the development of mouse muscle spindles. Neuroreport 9(5):905-9. [PubMed: 9579688]  [MGI Ref ID J:47110]

Stucky CL; Shin JB; Lewin GR. 2002. Neurotrophin-4: a survival factor for adult sensory neurons. Curr Biol 12(16):1401-4. [PubMed: 12194821]  [MGI Ref ID J:78592]

Ntf3^tm1Jae related

Asztely F; Kokaia M; Olofsdotter K; Ortegren U; Lindvall O. 2000. Afferent-specific modulation of short-term synaptic plasticity by neurotrophins in dentate gyrus. Eur J Neurosci 12(2):662-9. [PubMed: 10712646]  [MGI Ref ID J:108125]

Botchkarev VA; Botchkarev NV; Albers KM; van der Veen C; Lewin GR; Paus R. 1998. Neurotrophin-3 involvement in the regulation of hair follicle morphogenesis. J Invest Dermatol 111(2):279-85. [PubMed: 9699730]  [MGI Ref ID J:65041]

Botchkarev VA; Welker P; Albers KM; Botchkareva NV; Metz M; Lewin GR; Bulfone-Paus S; Peters EM; Lindner G; Paus R. 1998. A new role for neurotrophin-3: involvement in the regulation of hair follicle regression (catagen). Am J Pathol 153(3):785-99. [PubMed: 9736028]  [MGI Ref ID J:49792]

Canals JM; Pineda JR; Torres-Peraza JF; Bosch M; Martin-Ibanez R; Munoz MT; Mengod G; Ernfors P; Alberch J. 2004. Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. J Neurosci 24(35):7727-39. [PubMed: 15342740]  [MGI Ref ID J:92634]

ElShamy WM; Ernfors P. 1996. A local action of neurotrophin-3 prevents the death of proliferating sensory neuron precursor cells. Neuron 16(5):963-72. [PubMed: 8630254]  [MGI Ref ID J:33221]

ElShamy WM; Ernfors P. 1997. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 complement and cooperate with each other sequentially during visceral neuron development. J Neurosci 17(22):8667-75. [PubMed: 9348335]  [MGI Ref ID J:44086]

ElShamy WM; Fridvall LK; Ernfors P. 1998. Growth arrest failure, G1 restriction point override, and S phase death of sensory precursor cells in the absence of neurotrophin-3. Neuron 21(5):1003-15. [PubMed: 9856457]  [MGI Ref ID J:51430]

ElShamy WM; Linnarsson S; Lee KF; Jaenisch R; Ernfors P. 1996. Prenatal and postnatal requirements of NT-3 for sympathetic neuroblast survival and innervation of specific targets. Development 122(2):491-500. [PubMed: 8625800]  [MGI Ref ID J:69121]

Elmer E; Kokaia M; Ernfors P; Ferencz I; Kokaia Z; Lindvall O. 1997. Suppressed kindling epileptogenesis and perturbed BDNF and TrkB gene regulation in NT-3 mutant mice. Exp Neurol 145(1):93-103. [PubMed: 9184113]  [MGI Ref ID J:40463]

Ernfors P; Van De Water T; Loring J; Jaenisch R. 1995. Complementary roles of BDNF and NT-3 in vestibular and auditory development. Neuron 14(6):1153-64. [PubMed: 7605630]  [MGI Ref ID J:26749]

Fan G; Copray S; Huang EJ; Jones K; Yan Q; Walro J; Jaenisch R; Kucera J. 2000. Formation of a full complement of cranial proprioceptors requires multiple neurotrophins. Dev Dyn 218(2):359-70. [PubMed: 10842362]  [MGI Ref ID J:62766]

Fan G; Jaenisch R; Kucera J. 1999. A role for p75 receptor in neurotrophin-3 functioning during the development of limb proprioception. Neuroscience 90(1):259-68. [PubMed: 10188952]  [MGI Ref ID J:53825]

Fan L; Girnius S; Oakley B. 2004. Support of trigeminal sensory neurons by nonneuronal p75 neurotrophin receptors. Brain Res Dev Brain Res 150(1):23-39. [PubMed: 15126035]  [MGI Ref ID J:90280]

Fundin BT; Silos-Santiago I; Ernfors P; Fagan AM; Aldskogius H ; DeChiara TM ; Phillips HS ; Barbacid M ; Yancopoulos GD ; Rice FL. 1997. Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and P75 LNGFR. Dev Biol 190(1):94-116. [PubMed: 9331334]  [MGI Ref ID J:43425]

Gacek RR; Khetarpal U. 1998. Neurotrophin 3, not brain-derived neurotrophic factor or neurotrophin 4, knockout mice have delay in vestibular compensation after unilateral labyrinthectomy. Laryngoscope 108(5):671-8. [PubMed: 9591544]  [MGI Ref ID J:113175]

Holm PC; Rodriguez FJ; Kresse A; Canals JM; Silos-Santiago I; Arenas E. 2003. Crucial role of TrkB ligands in the survival and phenotypic differentiation of developing locus coeruleus noradrenergic neurons. Development 130(15):3535-45. [PubMed: 12810600]  [MGI Ref ID J:83661]

Kokaia M; Asztely F; Olofsdotter K; Sindreu CB; Kullmann DM; Lindvall O. 1998. Endogenous neurotrophin-3 regulates short-term plasticity at lateral perforant path-granule cell synapses. J Neurosci 18(21):8730-9. [PubMed: 9786980]  [MGI Ref ID J:50620]

Krimm RF; Davis BM; Albers KM. 2000. Cutaneous overexpression of neurotrophin-3 (NT3) selectively restores sensory innervation in NT3 gene knockout mice. J Neurobiol 43(1):40-9. [PubMed: 10756065]  [MGI Ref ID J:62390]

Kucera J; Fan G; Walro J; Copray S; Tessarollo L; Jaenisch R. 1998. Neurotrophin-3 and trkC in muscle are non-essential for the development of mouse muscle spindles. Neuroreport 9(5):905-9. [PubMed: 9579688]  [MGI Ref ID J:47110]

Liu X; Jaenisch R. 2000. Severe peripheral sensory neuron loss and modest motor neuron reduction in mice with combined deficiency of brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5. Dev Dyn 218(1):94-101. [PubMed: 10822262]  [MGI Ref ID J:62072]

McIlwrath SL; Hu J; Anirudhan G; Shin JB; Lewin GR. 2005. The sensory mechanotransduction ion channel ASIC2 (acid sensitive ion channel 2) is regulated by neurotrophin availability. Neuroscience 131(2):499-511. [PubMed: 15708491]  [MGI Ref ID J:105150]

Nosrat CA; Blomlof J; ElShamy WM; Ernfors P; Olson L. 1997. Lingual deficits in BDNF and NT3 mutant mice leading to gustatory and somatosensory disturbances, respectively. Development 124(7):1333-42. [PubMed: 9118804]  [MGI Ref ID J:40033]

Olofsdotter K; Lindvall O; Asztely F. 2000. Increased synaptic inhibition in dentate gyrus of mice with reduced levels of endogenous brain-derived neurotrophic factor. Neuroscience 101(3):531-9. [PubMed: 11113302]  [MGI Ref ID J:118727]

Patel TD; Kramer I; Kucera J; Niederkofler V; Jessell TM; Arber S; Snider WD. 2003. Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents. Neuron 38(3):403-16. [PubMed: 12741988]  [MGI Ref ID J:83461]

Raab M; Worl J; Brehmer A; Neuhuber WL. 2003. Reduction of NT-3 or TrkC results in fewer putative vagal mechanoreceptors in the mouse esophagus. Auton Neurosci 108(1-2):22-31. [PubMed: 14614961]  [MGI Ref ID J:102715]

Rice FL; Albers KM; Davis BM; Silos-Santiago I; Wilkinson GA; LeMaster AM; Ernfors P; Smeyne RJ; Aldskogius H; Phillips HS; Barbacid M; DeChiara TM; Yancopoulos GD; Dunne CE; Fundin BT. 1998. Differential dependency of unmyelinated and A delta epidermal and upper dermal innervation on neurotrophins, trk receptors, and p75LNGFR. Dev Biol 198(1):57-81. [PubMed: 9640332]  [MGI Ref ID J:107715]

Sahenk Z; Oblinger J; Edwards C. 2008. Neurotrophin-3 deficient Schwann cells impair nerve regeneration. Exp Neurol 212(2):552-6. [PubMed: 18511043]  [MGI Ref ID J:137927]

Sedy J; Szeder V; Walro JM; Ren ZG; Nanka O; Tessarollo L; Sieber-Blum M; Grim M; Kucera J. 2004. Pacinian corpuscle development involves multiple Trk signaling pathways. Dev Dyn 231(3):551-63. [PubMed: 15376326]  [MGI Ref ID J:93853]

Sheard PW; Musaad K; Duxson MJ. 2002. Distribution of neurotrophin receptors in the mouse neuromuscular system. Int J Dev Biol 46(4):569-75. [PubMed: 12141445]  [MGI Ref ID J:100050]

Story GM; DiCarlo SE; Rodenbaugh DW; Dluzen DE; Kucera J; Maron MB; Walro JM. 2000. Inactivation of one copy of the mouse neurotrophin-3 gene induces cardiac sympathetic deficits Physiol Genomics 2(3):129-36. [PubMed: 11015591]  [MGI Ref ID J:62748]

Stucky CL; Shin JB; Lewin GR. 2002. Neurotrophin-4: a survival factor for adult sensory neurons. Curr Biol 12(16):1401-4. [PubMed: 12194821]  [MGI Ref ID J:78592]

Torres-Peraza J; Pezzi S; Canals JM; Gavalda N; Garcia-Martinez JM; Perez-Navarro E; Alberch J. 2007. Mice heterozygous for neurotrophin-3 display enhanced vulnerability to excitotoxicity in the striatum through increased expression of N-methyl-D-aspartate receptors. Neuroscience 144(2):462-71. [PubMed: 17081696]  [MGI Ref ID J:117952]

Woolley A; Sheard P; Dodds K; Duxson M. 1999. Alpha motoneurons are present in normal numbers but with reduced soma size in neurotrophin-3 knockout mice. Neurosci Lett 272(2):107-10. [PubMed: 10507553]  [MGI Ref ID J:59763]

Woolley AG; Sheard PW; Duxson MJ. 2005. Neurotrophin-3 null mutant mice display a postnatal motor neuropathy. Eur J Neurosci 21(8):2100-10. [PubMed: 15869506]  [MGI Ref ID J:101071]

Wright DE; Zhou L; Kucera J; Snider WD. 1997. Introduction of a neurotrophin-3 transgene into muscle selectively rescues proprioceptive neurons in mice lacking endogenous neurotrophin-3. Neuron 19(3):503-17. [PubMed: 9331344]  [MGI Ref ID J:43444]

Wyatt S; Pinon LG; Ernfors P; Davies AM. 1997. Sympathetic neuron survival and TrkA expression in NT3-deficient mouse embryos. EMBO J 16(11):3115-23. [PubMed: 9214629]  [MGI Ref ID J:41123]

Zhang C; Brandemihl A; Lau D; Lawton A; Oakley B. 1997. BDNF is required for the normal development of taste neurons in vivo. Neuroreport 8(4):1013-7. [PubMed: 9141083]  [MGI Ref ID J:40246]

elshamy WM; Ernfors P. 1996. Requirement of neurotrophin-3 for the survival of proliferating trigeminal ganglion progenitor cells. Development 122(8):2405-14. [PubMed: 8756286]  [MGI Ref ID J:34771]

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 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
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

See Terms of Use

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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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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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

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.