Strain Name:

B6.129P2-Nppatm1Unc/J

Stock Number:

002685

Availability:

Repository-Cryopreserved

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 129P2 via E14TG2a ES cell line
GenerationN17pN1 (08-JAN-04)
 
Donating Investigator Oliver Smithies,   University of North Carolina

Appearance
black
Related Genotype: a/a

Description
Homozygotes are viable and fertile. Homozygotes show elevated blood pressure on both high and low salt diets. Heterozygous mice show normal blood pressure on a low salt diet but elevated blood pressue on a high salt diet.

Control Information

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

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

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

Nppatm1Unc/Nppa+

        involves: 129P2/OlaHsd * C57BL/6J
  • cardiovascular system phenotype
  • increased blood pressure (MGI Ref ID J:64898)
    • after a 5-wk hypoxic exposure (10% O2), hypoxia-induced increases in right ventricular (RV) pressure are significantly higher in heterozygous than in wild-type mice (63±7% vs. 45±10%, respectively)
    • salt-sensitive hypertension (MGI Ref ID J:76312)
      • when fed on standard chow (0.8% NaCl) for 2 weeks, heterozygotes display normal blood pressures and normal heart rates relative to wild-type
      • when fed on high salt chow (8% NaCl) for 2 weeks, heterozygotes become hypertensive, with blood pressures elevated by 27 mm Hg relative to wild-type; heart rates remain unaffected relative to wild-type
  • right ventricle hypertrophy (MGI Ref ID J:64898)
    • after a 5-wk hypoxic exposure (10% O2), hypoxia-induced increases in RV mass are significantly higher in heterozygous than in wild-type (29±4% vs. 26±5%, respectively)

Nppatm1Unc/Nppatm1Unc

        involves: 129P2/OlaHsd * C57BL/6
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype (MGI Ref ID J:54986)
    • homozygotes show no differences in body weight or hematocrit relative to wild-type mice under both normoxic and chronically hypoxic conditions
    • abnormal cardiovascular system physiology (MGI Ref ID J:53877)
      • autonomic ganglion blockade induces comparable % reductions in CO, HR, and stroke volume in both genotypes; however, in mutants, the concomitant decrease in ABP (%) is significantly higher than in wild-type mice and is accompanied by a significant reduction in total peripheral resistance
      • abnormal blood pressure (MGI Ref ID J:63072)
        • intracerebroventricular ANP or losartan results in significant (and rapid) hypotension only in homozygous mutant mice
        • notably, mutant and wild-type mice show comparable reductions in mean ABP after intravenous injection of vasopressin V1-receptor antagonist, suggesting that increased central AT1-receptor activation, but not systemic vasopressin, sustains chronic hypertension in mutant mice
        • increased blood pressure (MGI Ref ID J:64898)
          • after a 5-wk hypoxic exposure (10% O2), hypoxia-induced increases in right ventricular (RV) pressure are significantly higher in homozygous than in wild-type mice (104±17% vs. 45±10%, respectively)
          • under normoxic conditions, homozygotes exhibit higher right ventricular peak pressure (RVPP) than wild-type mice
          • after 3 weeks of hypoxia, homozygotes show a higher RVPP than heterozygous or wild-type mice
          • hypertension (MGI Ref ID J:76312)
            • homozygotes exhibit significant increases in blood pressures (8 to 23 mm Hg) when they are fed standard (0.5% NaCl) and intermediate (2% NaCl) salt diets for 2-3 weeks
            • the heart rates of homozygotes are comparable to those of wild-type and heterozygous littermates
            • salt-sensitive hypertension (MGI Ref ID J:57623)
              • when fed on a HS-diet (8% NaCl) for 4 weeks, homozygotes exhibit significantly increased basal arterial blood pressures (139±5 mm Hg) relative to wild-type mice (82±1 mm Hg)
              • chronic treatment with the AT1 antagonist losartan has no effect on ABP in wild-type mice, but reduces ABP to wild-type levels in salt-fed mutant mice
              • regardless of the state of alertness (i.e. conscious vs. anesthetized), homozygotes develop salt-sensitive hypertension (135±3 mm Hg) after prolonged maintenance (>1 wk) on a high-salt (HS; 8% NaCl) diet compared with both homozygotes (115±2 mm Hg) and wild-type (110±5 mm Hg) mice maintained on a low-salt (LS; 0.008% NaCl) diet
          • increased diastolic blood pressure (MGI Ref ID J:53877)
            • homozygotes display elevated baseline arterial blood pressure (132±4 mm Hg) relative to wild-type mice (95±2 mm Hg)
      • abnormal vascular resistance (MGI Ref ID J:53877)
        • chronically hypertensive homozygotes exhibit elevated baseline total peripheral resistance relative to normotensive wild-type mice; no differences in stroke volume are observed
      • decreased cardiac output (MGI Ref ID J:53877)
        • homozygotes display a tendency towards reduced cardiac output (CO) values, as a result of reduced basal heart rate (HR); however, the differences in basal CO and HR do not reach statistical significance
      • increased heart rate (MGI Ref ID J:57623)
        • when fed on a HS-diet (8% NaCl) for 4 weeks, homozygotes exhibit significantly increased basal heart rates (504± 20 beats/min) relative to wild-type (425±25 beats/min)
        • chronic treatment with the AT1 antagonist losartan has no effect on HR in wild-type mice, but reduces HR to wild-type levels in salt-fed mutant mice
      • pulmonary hypertension (MGI Ref ID J:54986)
        • homozygotes develop severe hypoxic pulmonary hypertension, as shown by significant differences in RVPP, RV/BW, RV/LV+S, or % of muscularized pulmonary vessels between hypoxia-adapted homozygotes and wild-type mice
    • abnormal vascular smooth muscle morphology (MGI Ref ID J:54986)
      • under both normoxic and hypoxic conditions, homozygotes display a higher % of muscularized peripheral pulmonary vessels relative to heterozygous or wild-type mice
      • under normoxic conditions, homozygotes exhibit a higher % of partially muscularized peripheral pulmonary vessels
      • after 3 weeks of hypobaric hypoxia, homozygotes exhibit a higher % of fully muscularized peripheral pulmonary vessels
    • enlarged heart (MGI Ref ID J:76312)
      • on intermediate salt diets (2% NaCl), homozygotes exhibit cardiac enlargement relative to wild-type
      • increased heart weight (MGI Ref ID J:76312)
        • on intermediate salt diets (2% NaCl), homozygotes exhibit a greater ratio of heart weight to body weight than both heterozygous and wild-type
      • left ventricle hypertrophy (MGI Ref ID J:54986)
        • under normoxic and chronically hypoxic conditions, homozygotes display a higher left ventricle plus septum weight-to-body weight (LV+S/BW) ratio than heterozygous and wild-type mice
        • compared with wild-type, (LV+S/BW) is 49% and 38% greater in homozygotes kept in normoxic and chronically hypoxic conditions, respectively
      • right ventricle hypertrophy (MGI Ref ID J:54986)
        • under normoxic and chronically hypoxic conditions, homozygotes display a higher right ventricle weight-to-body weight (RV/BW) ratio than heterozygous and wild-type mice
        • compared with wild-type, RV/BW is 60% and 53% greater in homozygotes kept in normoxic and chronically hypoxic conditions, respectively
        • notably, the RV/LV+S ratio is higher in homozygous mutants than that in heterozygous or wild-type mice under hypoxic but not under normoxic conditions
        • after a 5-wk hypoxic exposure (10% O2), hypoxia-induced increases in RV mass are significantly higher in homozygous than in wild-type (38±4% vs. 26±5%, respectively)
  • hematopoietic system phenotype
  • decreased hematocrit (MGI Ref ID J:76312)
    • after 2 wk on a high-salt diet, homozygotes exhibit significantly reduced hematocrits relative to wild-type mice, suggesting relative salt-retention during chronic high-salt maintainance
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype (MGI Ref ID J:57623)
    • homozygotes fed on a HS-diet (8% NaCl) for 4 weeks, display a comparable cumulative dietary intake of food and water and urinary excretion of fluid and electrolytes relative to wild-type; chronic treatment with losartan has no effect on these parameters
    • abnormal renin activity (MGI Ref ID J:95900)
      • in homozygotes maintained on a high-salt (HS; 8% NaCl) diet, the salt-sensitive hypertensive response is time-dependent (>1 wk latency), and is associated with failure to downregulate plasma renin activity (PRA)
      • in contrast, wild-type mice respond to HS diet with an appropriate reduction in PRA relative to wild-type mice maintained on low-salt diet (LS; 0.008% NaCl), and remain normotensive for the duration of the dietary regimen
    • increased circulating adrenaline level (MGI Ref ID J:57623)
      • when fed on a HS-diet (8% NaCl) for 4 weeks, homozygotes exhibit a 10-fold increase in baseline total plasma catecholamine levels (norepinephrine plus epinephrine) relative to wild-type mice, indicating an abnormally elevated sympathetic tone
      • chronic treatment with the AT1 antagonist losartan reduces plasma catecholamine to approximately wild-type levels in salt-fed mutant mice
      • notably, plasma aldosterone does not differ significantly between genotypes and is not altered by losartan
    • increased circulating sodium level (MGI Ref ID J:95900)
      • after 2 wk on 8% NaCl, homozygotes show increased sodium reabsorption relative to wild-type mice [unpublished]
  • muscle phenotype
  • abnormal vascular smooth muscle morphology (MGI Ref ID J:54986)
    • under both normoxic and hypoxic conditions, homozygotes display a higher % of muscularized peripheral pulmonary vessels relative to heterozygous or wild-type mice
    • under normoxic conditions, homozygotes exhibit a higher % of partially muscularized peripheral pulmonary vessels
    • after 3 weeks of hypobaric hypoxia, homozygotes exhibit a higher % of fully muscularized peripheral pulmonary vessels
  • respiratory system phenotype
  • pulmonary hypertension (MGI Ref ID J:54986)
    • homozygotes develop severe hypoxic pulmonary hypertension, as shown by significant differences in RVPP, RV/BW, RV/LV+S, or % of muscularized pulmonary vessels between hypoxia-adapted homozygotes and wild-type mice
View Research Applications

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

Nppatm1Unc related

Cardiovascular Research
Hypertension (diet-induced)

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Nppatm1Unc
Allele Name targeted mutation 1, University of North Carolina
Allele Type Targeted (knock-out)
Common Name(s) ANP-; proANP-;
Mutation Made By Oliver Smithies,   University of North Carolina
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14TG2a
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Nppa, natriuretic peptide precursor type A
Chromosome 4
Gene Common Name(s) ANF; ANP; ATFB6; Anf; CDD-ANF; PND; Pnd; RATANF; atrial natriuretic peptide; natriuretic peptide precursor A;
General Note Phenotypic Similarity to Human Syndrome: Salt-Sensitive Hypertension (J:76312).
Molecular Note 11 bp of exon 2 was replaced with a neomycin resistance gene via homologous recombination. Radioimmunoassay of plasma and atria from homozygous mutant animals did not detect protein product. [MGI Ref ID J:76312]

Genotyping

Genotyping Information

Genotyping Protocols

Nppatm1Unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

John SW; Krege JH; Oliver PM; Hagaman JR; Hodgin JB; Pang SC; Flynn TG; Smithies O. 1995. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science 267(5198):679-81. [PubMed: 7839143]  [MGI Ref ID J:76312]

Additional References

Sun JZ; Chen SJ; Majid-Hasan E; Oparil S; Chen YF. 2002. Dietary salt supplementation selectively downregulates NPR-C receptor expression in kidney independently of ANP. Am J Physiol Renal Physiol 282(2):F220-7. [PubMed: 11788435]  [MGI Ref ID J:75607]

Nppatm1Unc related

Ackermann U; Azizi N. 2000. Increased central AT(1)-receptor activation, not systemic vasopressin, sustains hypertension in ANP knockout mice. Am J Physiol Regul Integr Comp Physiol 278(6):R1441-5. [PubMed: 10848509]  [MGI Ref ID J:63072]

Feng JA; Perry G; Mori T; Hayashi T; Oparil S; Chen YF. 2003. Pressure-independent enhancement of cardiac hypertrophy in atrial natriuretic peptide-deficient mice. Clin Exp Pharmacol Physiol 30(5-6):343-9. [PubMed: 12859424]  [MGI Ref ID J:103080]

Franco V; Chen YF; Oparil S; Feng JA; Wang D; Hage F; Perry G. 2004. Atrial natriuretic peptide dose-dependently inhibits pressure overload-induced cardiac remodeling. Hypertension 44(5):746-50. [PubMed: 15452027]  [MGI Ref ID J:103584]

Honrath U; Chong CK; Melo LG; Sonnenberg H. 1999. Effect of saline infusion on kidney and collecting duct function in atrial natriuretic peptide (ANP) gene 'knockout' mice. Can J Physiol Pharmacol 77(6):454-7. [PubMed: 10537232]  [MGI Ref ID J:57410]

John SW; Veress AT; Honrath U; Chong CK; Peng L; Smithies O; Sonnenberg H. 1996. Blood pressure and fluid-electrolyte balance in mice with reduced or absent ANP. Am J Physiol 271(1 Pt 2):R109-14. [PubMed: 8760210]  [MGI Ref ID J:113046]

Klinger JR; Warburton RR; Pietras LA; Smithies O; Swift R; Hill NS. 1999. Genetic disruption of atrial natriuretic peptide causes pulmonary hypertension in normoxic and hypoxic mice. Am J Physiol 276(5 Pt 1):L868-74. [PubMed: 10330043]  [MGI Ref ID J:54986]

Li P; Wang D; Lucas J; Oparil S; Xing D; Cao X; Novak L; Renfrow MB; Chen YF. 2008. Atrial natriuretic peptide inhibits transforming growth factor beta-induced Smad signaling and myofibroblast transformation in mouse cardiac fibroblasts. Circ Res 102(2):185-92. [PubMed: 17991884]  [MGI Ref ID J:141565]

Melo LG; Veress AT; Ackermann U; Pang SC; Flynn TG; Sonnenberg H. 1999. Chronic hypertension in ANP knockout mice: contribution of peripheral resistance. Regul Pept 79(2-3):109-15. [PubMed: 10100923]  [MGI Ref ID J:53877]

Melo LG; Veress AT; Ackermann U; Steinhelper ME; Pang SC; Tse Y; Sonnenberg H. 1999. Chronic regulation of arterial blood pressure in ANP transgenic and knockout mice: role of cardiovascular sympathetic tone. Cardiovasc Res 43(2):437-44. [PubMed: 10536674]  [MGI Ref ID J:59693]

Melo LG; Veress AT; Chong CK; Ackermann U; Sonnenberg H. 1999. Salt-sensitive hypertension in ANP knockout mice is prevented by AT1 receptor antagonist losartan. Am J Physiol 277(3 Pt 2):R624-30. [PubMed: 10484477]  [MGI Ref ID J:57623]

Melo LG; Veress AT; Chong CK; Pang SC; Flynn TG; Sonnenberg H. 1998. Salt-sensitive hypertension in ANP knockout mice: potential role of abnormal plasma renin activity. Am J Physiol 274(1 Pt 2):R255-61. [PubMed: 9458926]  [MGI Ref ID J:95900]

Mori T; Chen YF; Feng JA; Hayashi T; Oparil S; Perry GJ. 2004. Volume overload results in exaggerated cardiac hypertrophy in the atrial natriuretic peptide knockout mouse. Cardiovasc Res 61(4):771-9. [PubMed: 14985074]  [MGI Ref ID J:102124]

O'Tierney PF; Tse MY; Pang SC. 2007. Elevated renal norepinephrine in proANP gene-disrupted mice is associated with increased tyrosine hydroxylase expression in sympathetic ganglia. Regul Pept 143(1-3):90-6. [PubMed: 17482290]  [MGI Ref ID J:136761]

Sangaralingham SJ; Tse MY; Pang SC. 2007. Estrogen protects against the development of salt-induced cardiac hypertrophy in heterozygous proANP gene-disrupted mice. J Endocrinol 194(1):143-152. [PubMed: 17592028]  [MGI Ref ID J:122390]

Sun JZ; Chen SJ; Li G; Chen YF. 2000. Hypoxia reduces atrial natriuretic peptide clearance receptor gene expression in ANP knockout mice. Am J Physiol Lung Cell Mol Physiol 279(3):L511-9. [PubMed: 10956626]  [MGI Ref ID J:64898]

Sun JZ; Chen SJ; Majid-Hasan E; Oparil S; Chen YF. 2002. Dietary salt supplementation selectively downregulates NPR-C receptor expression in kidney independently of ANP. Am J Physiol Renal Physiol 282(2):F220-7. [PubMed: 11788435]  [MGI Ref ID J:75607]

Vera N; Tse MY; Watson JD; Sarda S; Steinhelper ME; John SW; Flynn TG; Pang SC. 2000. Altered expression of natriuretic peptide receptors in proANP gene disrupted mice. Cardiovasc Res 46(3):595-603. [PubMed: 10912470]  [MGI Ref ID J:84437]

Wang D; Oparil S; Feng JA; Li P; Perry G; Chen LB; Dai M; John SW; Chen YF. 2003. Effects of pressure overload on extracellular matrix expression in the heart of the atrial natriuretic peptide-null mouse. Hypertension 42(1):88-95. [PubMed: 12756220]  [MGI Ref ID J:102952]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Price (US dollars $)
Cryorecovery Fee $1900.00
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.

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Price (US dollars $)
Cryorecovery Fee $2470.00
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.

Additional Supply Details

Supply Details

Standard SupplyCryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks.

    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


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