Strain Name:

STOCK Tg(Cga-LHB/CGB)94Jhn/J

Stock Number:

006619

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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 Mutant Stock; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation?+F1p
Generation Definitions
 
Donating Investigator John Nilson,   Washington State University

Description
Hemizygous females are not fertile and hemizygous males are sub-fertile. Hemizygotes hypersecrete luteinizing hormone (LH) from pituitary gonadotropes under hypothalamic control. Inclusion of a bovine luteinizing hormone beta (LHB) sequence in the transgene results in a longer hormone half-life. Transgenic females display a range of reproductive and endocrine anomalies, while males are largely phenotypically normal. Transgenic males do not have elevated serum LH or testosterone when compared to wildtype animals, although their testes are significantly smaller. Transgenic females display elevated serum LH, androgens, and estrogens, with subsequent phenotypes including infertility with chronic anovulation and ovarian pathologies ranging from ovarian cysts to strain-dependent granulosa and theca-interstitial cell tumors. Tumors have been noted in mice from age 4 to 9 months. Other major phenotypes include hyperandrogenemia and precocious puberty, defects in uterine receptivity and mid-gestation pregnancy failure, increased oocyte congression failure, adrenocortical hyperfunction, increased central obesity, pituitary adenomas, mammary gland hyperplasia, cancer predisposition, and renal abnormalities (enlarged bladders, dilated ureters, hydronephrosis, nephritis).<br> In humans, LH hypersecretion is implicated in infertility, miscarriages, and development of granulosa cell tumors. This transgenic mouse is a unique model that permits the study of underlying mechanisms of LH toxicity as female transgenic animals display similar reproductive and endocrine pathologies. The female is a model of functional ovarian hyperstimulation, and displays many of the specific endocrine attributes of polycystic ovarian syndrome (PCOS), granulosa cell tumor formation, and central precocious puberty.

Development
The transgene consists of the entire bovine luteinizing hormone beta (LHB) cDNA fused in-frame to the last 87 bp of the human chorionic gonadotropin beta gene (CGB) encoding the carboxy terminal peptide (CTP), whose expression is driven by the bovine glycoprotein hormone alpha (CGA) promoter (positions -315 to +45). The construct was initially injected into C57BL/6 x SJL F1 hybrid embryos, but foundation animals were crossed subsequently to outbred CF-1 females for more than ten generations.

Control Information

  Control
   Noncarrier
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of LHB
009643   B6.Cg-Tg(Lhb-cre)1Sac/J
View Strains carrying other alleles of LHB     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Tg(Cga-LHB/CGB)94Jhn/?

        involves: C57BL/6 * SJL
  • reproductive system phenotype
  • anovulation
    • 12-16 week old female mice fail to ovulate   (MGI Ref ID J:55157)
    • female mice fail to ovulate even when ovulation is tried to be forced through pseudopregnancy   (MGI Ref ID J:55157)
  • delayed male fertility
    • some males breed after prolonged delays   (MGI Ref ID J:55157)
  • enlarged ovary
    • some of the females have enlarged ovaries that are packed with corpora lutea   (MGI Ref ID J:55157)
    • progesterone levels are elevated in these mice   (MGI Ref ID J:55157)
  • impaired luteal cell differentiation
    • luteal cells have a prolonged lifespan, with pseudopregnant female mice having elevated progesterone levels for 18 days compared to less than 12 days for littermate controls   (MGI Ref ID J:55157)
  • ovary cysts
    • some mice have numerous cysts in their ovaries that are hemorrhagic or fluid filled and derived from both follicular and luteal tissue   (MGI Ref ID J:55157)
    • cystic ovaries have increased blood flow to the tissue   (MGI Ref ID J:55157)
    • testosterone and estradiol levels are elevated in these mice   (MGI Ref ID J:55157)
  • reduced female fertility
    • only 1 female of 9 that mated multiple times was able to produce a litter   (MGI Ref ID J:55157)
  • reduced male fertility
    • male mice have reduced fertility with some males never breeding and others breeding after prolonged delays   (MGI Ref ID J:55157)
  • small testis
    • testes in transgenic males is significantly smaller than in controls   (MGI Ref ID J:55157)
  • tumorigenesis
  • increased ovary tumor incidence
    • a subset of transgenic females develop ovarian granulose and theca-interstitial cell tumors by 4-8 months of age   (MGI Ref ID J:55157)
    • these tumors contain varying amounts of other stromal cells and have an increased blood supply   (MGI Ref ID J:55157)
  • renal/urinary system phenotype
  • dilated ureter
    • about 25% of infertile females have dilated ureters associated with hydronephrosis of the kidneys   (MGI Ref ID J:55157)
  • distended urinary bladder
    • about 25% of infertile females have enlarged bladders associated with hydronephrosis of the kidneys   (MGI Ref ID J:55157)
  • hydronephrosis
    • about 25% of infertile females have hydronephrosis of the kidneys   (MGI Ref ID J:55157)
    • in some mice the hydronephropathy is complicated by acute pyelonephritis whereas others have chronic interstitial nephritis   (MGI Ref ID J:55157)
  • pyelonephritis
    • in some mice the hydronephropathy is complicated by acute pyelonephritis   (MGI Ref ID J:55157)
  • tubulointerstitial nephritis
    • some mice develop chronic interstitial nephritis   (MGI Ref ID J:55157)
  • homeostasis/metabolism phenotype
  • increased circulating luteinizing hormone level
    • serum LH levels for female mice are elevated at 39.7 ng/ml compared to 2.7 ng/ml for littermate controls   (MGI Ref ID J:55157)
  • increased circulating progesterone level
    • transgenic females that have enlarged ovaries also have vastly elevated progesterone levels   (MGI Ref ID J:55157)
  • endocrine/exocrine gland phenotype
  • abnormal adrenocortical cell morphology
    • cells expressing markers of gonadal origin reside in the subcapsular zone of the adrenal cortex where stem cells normally reside   (MGI Ref ID J:125349)
    • these cells express high levels of phosphorylated Smad3   (MGI Ref ID J:125349)
  • enlarged ovary
    • some of the females have enlarged ovaries that are packed with corpora lutea   (MGI Ref ID J:55157)
    • progesterone levels are elevated in these mice   (MGI Ref ID J:55157)
  • impaired luteal cell differentiation
    • luteal cells have a prolonged lifespan, with pseudopregnant female mice having elevated progesterone levels for 18 days compared to less than 12 days for littermate controls   (MGI Ref ID J:55157)
  • ovary cysts
    • some mice have numerous cysts in their ovaries that are hemorrhagic or fluid filled and derived from both follicular and luteal tissue   (MGI Ref ID J:55157)
    • cystic ovaries have increased blood flow to the tissue   (MGI Ref ID J:55157)
    • testosterone and estradiol levels are elevated in these mice   (MGI Ref ID J:55157)
  • small testis
    • testes in transgenic males is significantly smaller than in controls   (MGI Ref ID J:55157)
  • immune system phenotype
  • pyelonephritis
    • in some mice the hydronephropathy is complicated by acute pyelonephritis   (MGI Ref ID J:55157)
  • tubulointerstitial nephritis
    • some mice develop chronic interstitial nephritis   (MGI Ref ID J:55157)
  • cellular phenotype
  • impaired luteal cell differentiation
    • luteal cells have a prolonged lifespan, with pseudopregnant female mice having elevated progesterone levels for 18 days compared to less than 12 days for littermate controls   (MGI Ref ID J:55157)
View Research Applications

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

Cancer Research
Increased Tumor Incidence
      Gonadal Tumors
      Gonadal Tumors: ovarian

Internal/Organ Research
Kidney Defects

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Cga-LHB/CGB)94Jhn
Allele Name transgene insertion 94, John H Nilson
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) LH-CTP; LHbeta-CTP; LHbetaCTP; Tg(bLHbeta-CTP)94Jhn; Tg-LHbeta;
Mutation Made By John Nilson,   Washington State University
Strain of Origin(C57BL/6 x SJL)F1
Expressed Gene CGB, chorionic gonadotropin, beta polypeptide, human
Expressed Gene LHB, luteinizing hormone beta polypeptide, bovine
Promoter Cga, glycoprotein hormones, alpha polypeptide, bovine
Molecular Note The transgene contains the entire bovine luteinizing hormone beta (LHB) cDNA fused to 87 bp encoding the c-terminal peptide (CTP) of the human chorionic gonadotropin beta subunit (CGB). The bovine glycoprotein hormone alpha subunit (CGA) promoter (positions -315 to +45) was used to drive expression in gonadotropes. Immunohistochemical analysis confirmed both LHB and CTP expression in the pituitaries. [MGI Ref ID J:55157]
 
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Cga-LHB/CGB)94Jhn, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Risma KA; Clay CM; Nett TM; Wagner T; Yun J; Nilson JH. 1995. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors. Proc Natl Acad Sci U S A 92(5):1322-6. [PubMed: 7877975]  [MGI Ref ID J:55157]

Additional References

Tg(Cga-LHB/CGB)94Jhn related

Beuschlein F; Looyenga BD; Bleasdale SE; Mutch C; Bavers DL; Parlow AF; Nilson JH; Hammer GD. 2003. Activin induces x-zone apoptosis that inhibits luteinizing hormone-dependent adrenocortical tumor formation in inhibin-deficient mice. Mol Cell Biol 23(11):3951-64. [PubMed: 12748296]  [MGI Ref ID J:83561]

Casadesus G; Milliken EL; Webber KM; Bowen RL; Lei Z; Rao CV; Perry G; Keri RA; Smith MA. 2007. Increases in luteinizing hormone are associated with declines in cognitive performance. Mol Cell Endocrinol 269(1-2):107-11. [PubMed: 17376589]  [MGI Ref ID J:126509]

Couse JF; Yates MM; Rodriguez KF; Johnson JA; Poirier D; Korach KS. 2006. The intraovarian actions of estrogen receptor-alpha are necessary to repress the formation of morphological and functional Leydig-like cells in the female gonad. Endocrinology 147(8):3666-78. [PubMed: 16627580]  [MGI Ref ID J:111680]

Couse JF; Yates MM; Sanford R; Nyska A; Nilson JH; Korach KS. 2004. Formation of cystic ovarian follicles associated with elevated luteinizing hormone requires estrogen receptor-beta. Endocrinology 145(10):4693-702. [PubMed: 15231698]  [MGI Ref ID J:92628]

Flaws JA; Abbud R; Mann RJ; Nilson JH; Hirshfield AN. 1997. Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary. Biol Reprod 57(5):1233-7. [PubMed: 9369192]  [MGI Ref ID J:163516]

Hodges CA; Ilagan A; Jennings D; Keri R; Nilson J; Hunt PA. 2002. Experimental evidence that changes in oocyte growth influence meiotic chromosome segregation. Hum Reprod 17(5):1171-80. [PubMed: 11980735]  [MGI Ref ID J:115500]

Keri RA; Lozada KL; Abdul-Karim FW; Nadeau JH; Nilson JH. 2000. Luteinizing hormone induction of ovarian tumors: oligogenic differences between mouse strains dictates tumor disposition. Proc Natl Acad Sci U S A 97(1):383-7. [PubMed: 10618427]  [MGI Ref ID J:59366]

Landis MD; Seachrist DD; Abdul-Karim FW; Keri RA. 2006. Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors. Oncogene 25(23):3325-34. [PubMed: 16434967]  [MGI Ref ID J:112325]

Looyenga BD; Hammer GD. 2007. Genetic removal of smad3 from inhibin-null mice attenuates tumor progression by uncoupling extracellular mitogenic signals from the cell cycle machinery. Mol Endocrinol 21(10):2440-57. [PubMed: 17652186]  [MGI Ref ID J:125349]

Looyenga BD; Wiater E; Vale W; Hammer GD. 2010. Inhibin-A antagonizes TGFbeta2 signaling by down-regulating cell surface expression of the TGFbeta coreceptor betaglycan. Mol Endocrinol 24(3):608-20. [PubMed: 20160125]  [MGI Ref ID J:157913]

Lyubarsky AL; Chen C; Simon MI; Pugh EN Jr. 2000. Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery of cone-driven retinal responses. J Neurosci 20(6):2209-17. [PubMed: 10704496]  [MGI Ref ID J:60964]

Mann RJ; Keri RA; Nilson JH. 2003. Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology. Recent Prog Horm Res 58:343-75. [PubMed: 12795427]  [MGI Ref ID J:84511]

Mann RJ; Keri RA; Nilson JH. 1999. Transgenic mice with chronically elevated luteinizing hormone are infertile due to anovulation, defects in uterine receptivity, and midgestation pregnancy failure. Endocrinology 140(6):2592-601. [PubMed: 10342846]  [MGI Ref ID J:66176]

Mikola M; Kero J; Nilson JH; Keri RA; Poutanen M; Huhtaniemi I. 2003. High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-alpha-subunit promoter/Simian virus 40 T-antigen fusion gene. Oncogene 22(21):3269-78. [PubMed: 12761497]  [MGI Ref ID J:83778]

Milliken EL; Ameduri RK; Landis MD; Behrooz A; Abdul-Karim FW; Keri RA. 2002. Ovarian Hyperstimulation by LH Leads to Mammary Gland Hyperplasia and Cancer Predisposition in Transgenic Mice. Endocrinology 143(9):3671-80. [PubMed: 12193583]  [MGI Ref ID J:78490]

Milliken EL; Lozada KL; Johnson E; Landis MD; Seachrist DD; Whitten I; Sutton AL; Abdul-Karim FW; Keri RA. 2008. Ovarian hyperstimulation induces centrosome amplification and aneuploid mammary tumors independently of alterations in p53 in a transgenic mouse model of breast cancer. Oncogene 27(12):1759-66. [PubMed: 17891171]  [MGI Ref ID J:135510]

Milliken EL; Zhang X; Flask C; Duerk JL; Macdonald PN; Keri RA. 2005. EB1089, a vitamin D receptor agonist, reduces proliferation and decreases tumor growth rate in a mouse model of hormone-induced mammary cancer. Cancer Lett 229(2):205-15. [PubMed: 16115727]  [MGI Ref ID J:101899]

Mohammad HP; Abbud RA; Parlow AF; Lewin JS; Nilson JH. 2003. Targeted overexpression of luteinizing hormone causes ovary-dependent functional adenomas restricted to cells of the Pit-1 lineage. Endocrinology 144(10):4626-36. [PubMed: 12960102]  [MGI Ref ID J:85766]

Nilson JH; Abbud RA; Keri RA; Quirk CC. 2000. Chronic hypersecretion of luteinizing hormone in transgenic mice disrupts both ovarian and pituitary function, with some effects modified by the genetic background Recent Prog Horm Res 55:69-89; discussion 89-91. [PubMed: 11036934]  [MGI Ref ID J:65359]

Owens GE; Keri RA; Nilson JH. 2002. Ovulatory Surges of Human CG Prevent Hormone-Induced Granulosa Cell Tumor Formation Leading to the Identification of Tumor-Associated Changes in the Transcriptome. Mol Endocrinol 16(6):1230-42. [PubMed: 12040011]  [MGI Ref ID J:76875]

Risma KA; Hirshfield AN; Nilson JH. 1997. Elevated luteinizing hormone in prepubertal transgenic mice causes hyperandrogenemia, precocious puberty, and substantial ovarian pathology. Endocrinology 138(8):3540-7. [PubMed: 9231809]  [MGI Ref ID J:66175]

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 & HusbandryWhen maintained as a live colony, Wildtype or outbred CF-1 female x Hemizygous male crosses are used. Hemizygous females are infertile and males are subfertile.

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.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

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 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.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

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 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
   Noncarrier
 
  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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