Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   01-MAR-06 Species laboratory mouse Generation N1F?+F19 (19-NOV-08) Generation Definitions   Donating Investigator Elaine Fuchs,   The Rockefeller University

Description
These mice possess loxP sites on either side of exon 3 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

When bred to a strain expressing Cre recombinase in the epithelial cells of the intestine (see Stock No. 004586 for example), this mutant mouse strain may be useful in studies of intestinal hyperplasia.

When bred to a strain expressing Cre recombinase in the podocytes of the kidney glomeruli (see Stock No. 008205 for example), this mutant mouse strain may be useful in studies of glomerular structural integrity.

Development
A loxP site flanked targeting vector containing neomycin resistance and phosphoglycerate kinase genes was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 3 of the targeted gene, and another loxP site was inserted upstream of exon 3. The construct was electroporated into 129X1/SvJ derived RW-4 embryonic stem (ES) cells which were transiently transfected with a vector containing the Cre-recombinase gene under the control of the cytomegalovirus promoter to remove the selection cassette. Correctly targeted ES cells were injected into C57BL/6J blastocysts.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Itgb1

003096

STOCK Itgb1tm1Lscd/J

View Strains carrying other alleles of Itgb1     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Itgb1^tm1Efu/Itgb1^tm1Efu Tg(NPHS2-cre)295Lbh/0

        involves: 129X1/SvJ * C57BL/6 * SJL   (conditional)

• mortality/aging
• premature death
  • only 10% of mice survived to 6 weeks of age   (MGI Ref ID J:135414)
  • 90% of mice were euthanized at 4-5 weeks of age due to end stage renal failure and nephrotic syndrome   (MGI Ref ID J:135414)
• behavior/neurological phenotype
• hypoactivity
  • mice become less physically active at 3 weeks of age   (MGI Ref ID J:135414)
• growth/size phenotype
• decreased body size
  • at 6 weeks of age, mice are smaller than control littermates   (MGI Ref ID J:135414)
• homeostasis/metabolism phenotype
• edema
  • mice develop severe edema at 3 weeks of age   (MGI Ref ID J:135414)
• increased urine protein level
  • mice develop severe proteinuria by 6 weeks of age   (MGI Ref ID J:135414)
• • albuminuria
    • albuminuria is already evident at P1   (MGI Ref ID J:135414)
    • marked albuminuria is noted at 6 weeks of age   (MGI Ref ID J:135414)
• renal/urinary system phenotype
• abnormal kidney morphology
  • mice develop end stage kidney disease with pathological changes in the glomeruli and tubulo-interstitium   (MGI Ref ID J:135414)
• • abnormal renal glomerular capsule morphology
    • at 6 weeks of age, many Bowmans capsules are either empty or contain partially degenerated glomeruli   (MGI Ref ID J:135414)
  • • podocyte foot process effacement
      • foot process effacement is first noted at E15.5   (MGI Ref ID J:135414)
      • extensive foot process effacement is noted at P10 and progresses by P21   (MGI Ref ID J:135414)
  • abnormal renal glomerulus basement membrane morphology
    • early segmental splitting of the glomerular basement membrane (GBM) is first noted at P10 and progresses by P21   (MGI Ref ID J:135414)
    • however, normal GBM morphogenesis is noted at E15.5 and at P1   (MGI Ref ID J:135414)
  • abnormal renal glomerulus morphology
    • at P21, mice exhibit degeneration of the capillary loops and mesangium with little glomerulosclerosis   (MGI Ref ID J:135414)
    • at 6 weeks of age, mice exhibit dilated glomerular capillaries and glomerular disintegration   (MGI Ref ID J:135414)
  • • abnormal glomerular capillary morphology
      • by P21, mice exhibit degeneration of the capillary loops   (MGI Ref ID J:135414)
      • however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1   (MGI Ref ID J:135414)
    • • dilated glomerular capillary
        • at P10, some glomeruli display segmentally "ballooned" capillary lumens; more "ballooned" capillary loops are noted at 3 weeks of age   (MGI Ref ID J:135414)
        • at 6 weeks of age, mice exhibit dilated glomerular capillaries   (MGI Ref ID J:135414)
    • expanded mesangial matrix
      • increased mesangial matrix with focal defects is noted at 3 weeks, indicating mesangial injury   (MGI Ref ID J:135414)
    • mesangial cell hyperplasia
      • mesangium hypercellularity is observed by 3 weeks of age   (MGI Ref ID J:135414)
    • mesangiolysis
      • multiple cytoplasmic vacuoles are first noted in mesangial cells at P10   (MGI Ref ID J:135414)
      • by P21, mice exhibit degeneration of the mesangium with little glomerulosclerosis   (MGI Ref ID J:135414)
  • abnormal renal tubule epithelium morphology
    • at P10, mice exhibit multiple cytoplasmic vacuoles within the tubular epithelial cells   (MGI Ref ID J:135414)
    • flattened epithelial cells with extensive proteinaceous tubular casts are noted at 6 weeks of age   (MGI Ref ID J:135414)
  • dilated renal tubules
    • dilated renal tubules containing hyaline material are observed at 6 weeks of age   (MGI Ref ID J:135414)
    • tubular dilatation is first evident at P10 and increased by 3 weeks of age   (MGI Ref ID J:135414)
  • pale kidney
    • at 6 weeks of age, end stage kidneys are paler than those of age-matched control mice   (MGI Ref ID J:135414)
  • renal cast
    • extensive proteinaceous tubular casts are noted at 6 weeks of age   (MGI Ref ID J:135414)
  • small kidney
    • at 6 weeks of age, end stage kidneys are smaller than those of age-matched control mice   (MGI Ref ID J:135414)
• increased podocyte apoptosis
  • a significant increase in podocyte apoptosis is detected at P10 and P21 by TUNEL analysis   (MGI Ref ID J:135414)
  • at P21, mice exhibit about one-third of the podocyte number found in control littermates, as quantified in EM sections   (MGI Ref ID J:135414)
• increased urine protein level
  • mice develop severe proteinuria by 6 weeks of age   (MGI Ref ID J:135414)
• • albuminuria
    • albuminuria is already evident at P1   (MGI Ref ID J:135414)
    • marked albuminuria is noted at 6 weeks of age   (MGI Ref ID J:135414)
• cardiovascular system phenotype
• abnormal glomerular capillary morphology
  • by P21, mice exhibit degeneration of the capillary loops   (MGI Ref ID J:135414)
  • however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1   (MGI Ref ID J:135414)
• • dilated glomerular capillary
    • at P10, some glomeruli display segmentally "ballooned" capillary lumens; more "ballooned" capillary loops are noted at 3 weeks of age   (MGI Ref ID J:135414)
    • at 6 weeks of age, mice exhibit dilated glomerular capillaries   (MGI Ref ID J:135414)
• cellular phenotype
• increased podocyte apoptosis
  • a significant increase in podocyte apoptosis is detected at P10 and P21 by TUNEL analysis   (MGI Ref ID J:135414)
  • at P21, mice exhibit about one-third of the podocyte number found in control littermates, as quantified in EM sections   (MGI Ref ID J:135414)

Itgb1^tm1Efu/Itgb1^tm1Efu Tg(Vil-cre)997Gum/0

        involves: 129X1/SvJ * C57BL/6J * SJL   (conditional)

• mortality/aging
• complete postnatal lethality
  • die between P7 and P14 from severe malnutrition   (MGI Ref ID J:119155)
• growth/size phenotype
• decreased body weight
  • by P4, mutants are less than half the body weight of controls   (MGI Ref ID J:119155)
• digestive/alimentary phenotype
• abnormal intestinal absorption
  • although mutants can feed, they are malnourished due to intestinal epithelium defects   (MGI Ref ID J:119155)
• abnormal intestine morphology
  • expansion of the intestinal stroma, muscularis, and extracellular matrix   (MGI Ref ID J:119155)
• • abnormal intestinal epithelium morphology
    • mutants exhibit an increase in intestinal epithelial cell proliferation in the crypts with dysplasia and polyps, resulting in an expanded epithelium   (MGI Ref ID J:119155)
    • the small intestinal epithelium shows a defective microvillus brush border on the apical surfaces of the villous enterocytes   (MGI Ref ID J:119155)
  • • abnormal crypts of Lieberkuhn morphology
      • intestinal crypt and villi expansion, enlargement, and dysplasia at P16   (MGI Ref ID J:119155)
      • crypt hyperplasia is most severe in the distal small intestine, proximal large intestine, and cecum   (MGI Ref ID J:119155)
    • abnormal enterocyte morphology
      • the intestinal epithelium shows large lipid inclusions within the villous enterocytes that are not seen in controls   (MGI Ref ID J:119155)
      • the intestinal microvilli are diminished in size and poorly formed, indicatiang defective enterocyte differentiation   (MGI Ref ID J:119155)
  • abnormal large intestine morphology
    • proximal large intestine is larger in external diameter than in controls   (MGI Ref ID J:119155)
  • abnormal small intestine morphology
    • distal small intestine is larger in external diameter than in controls   (MGI Ref ID J:119155)
  • intestine polyps
    • multiple juvenile-like polyps in the small intestinal mucosa   (MGI Ref ID J:119155)
• steatorrhea
  • fat malabsorption as indicated by the presence of large fat droplets in the intestinal contents   (MGI Ref ID J:119155)
• homeostasis/metabolism phenotype
• abnormal circulating lipid level
  • total serum lipid levels are reduced   (MGI Ref ID J:119155)
• endocrine/exocrine gland phenotype
• abnormal crypts of Lieberkuhn morphology
  • intestinal crypt and villi expansion, enlargement, and dysplasia at P16   (MGI Ref ID J:119155)
  • crypt hyperplasia is most severe in the distal small intestine, proximal large intestine, and cecum   (MGI Ref ID J:119155)

View Research Applications

Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Itgb1^tm1Efu related

Developmental Biology Research
Defects in Cell Adhesion Molecules
Embryonic Lethality (Homozygous)
Postnatal Lethality

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Itgb1tm1Efu
Allele Name		targeted mutation 1, Elaine Fuchs
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		CD29f; Itgb1f; Itgb1flox; beta1e3; beta1flox; integrin beta1flox;
Mutation Made By		Elaine Fuchs,   The Rockefeller University
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Itgb1, integrin beta 1 (fibronectin receptor beta)
Chromosome		8
Gene Common Name(s)		4633401G24Rik; AA409975; AA960159; CD29; ENSMUSG00000051907; FNRB; Fnrb; GPIIA; Gm9863; MDF2; MSK12; RIKEN cDNA 4633401G24 gene; VLA-BETA; VLAB; beta1 integrin; expressed sequence AA409975; expressed sequence AA960159; fibronectin receptor beta (integrin); predicted gene 9863; predicted gene, ENSMUSG00000051907;
Molecular Note		Insertion of loxP sites flanking the third exon of the Itgb1 gene. No effect on the function of the Itgb1 gene. [MGI Ref ID J:65039]

Genotyping

Genotyping Information

Genotyping Protocols

Itgb1^tm1Efu, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Raghavan S; Bauer C; Mundschau G; Li Q; Fuchs E. 2000. Conditional ablation of beta1 integrin in skin. Severe defects in epidermal proliferation, basement membrane formation, and hair follicle invagination. J Cell Biol 150(5):1149-60. [PubMed: 10974002]  [MGI Ref ID J:65039]

Additional References

Itgb1^tm1Efu related

Chan CS; Weeber EJ; Zong L; Fuchs E; Sweatt JD; Davis RL. 2006. Beta1-integrins are required for hippocampal AMPA receptor-dependent synaptic transmission, synaptic plasticity, and working memory. J Neurosci 26(1):223-32. [PubMed: 16399691]  [MGI Ref ID J:104150]

Chen H; Zou Z; Sarratt KL; Zhou D; Zhang M; Sebzda E; Hammer DA; Kahn ML. 2006. In vivo beta1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines. Genes Dev 20(8):927-32. [PubMed: 16618804]  [MGI Ref ID J:108331]

Chen J; Krasnow MA. 2012. Integrin Beta 1 suppresses multilayering of a simple epithelium. PLoS One 7(12):e52886. [PubMed: 23285215]  [MGI Ref ID J:195745]

DeNucci CC; Pagan AJ; Mitchell JS; Shimizu Y. 2010. Control of alpha4beta7 integrin expression and CD4 T cell homing by the beta1 integrin subunit. J Immunol 184(5):2458-67. [PubMed: 20118278]  [MGI Ref ID J:159655]

DeRouen MC; Zhen H; Tan SH; Williams S; Marinkovich MP; Oro AE. 2010. Laminin-511 and integrin beta-1 in hair follicle development and basal cell carcinoma formation. BMC Dev Biol 10:112. [PubMed: 21067603]  [MGI Ref ID J:166772]

Denucci CC; Shimizu Y. 2011. {beta}1 Integrin Is Critical for the Maintenance of Antigen-Specific CD4 T Cells in the Bone Marrow but Not Long-Term Immunological Memory. J Immunol 186(7):4019-26. [PubMed: 21357540]  [MGI Ref ID J:170691]

Di Paolo NC; Miao EA; Iwakura Y; Murali-Krishna K; Aderem A; Flavell RA; Papayannopoulou T; Shayakhmetov DM. 2009. Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity 31(1):110-21. [PubMed: 19576795]  [MGI Ref ID J:151628]

Frick A; Grammel D; Schmidt F; Poschl J; Priller M; Pagella P; von Bueren AO; Peraud A; Tonn JC; Herms J; Rutkowski S; Kretzschmar HA; Schuller U. 2012. Proper cerebellar development requires expression of beta1-integrin in Bergmann glia, but not in granule neurons. Glia 60(5):820-32. [PubMed: 22374686]  [MGI Ref ID J:181620]

Gao X; Eladari D; Leviel F; Tew BY; Miro-Julia C; Cheema F; Miller L; Nelson R; Paunescu TG; McKee M; Brown D; Al-Awqati Q. 2010. Deletion of hensin/DMBT1 blocks conversion of {beta}- to {alpha}-intercalated cells and induces distal renal tubular acidosis. Proc Natl Acad Sci U S A :. [PubMed: 21098262]  [MGI Ref ID J:167156]

Jones RG; Li X; Gray PD; Kuang J; Clayton F; Samowitz WS; Madison BB; Gumucio DL; Kuwada SK. 2006. Conditional deletion of beta1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality. J Cell Biol 175(3):505-14. [PubMed: 17088430]  [MGI Ref ID J:119155]

Kanasaki K; Kanda Y; Palmsten K; Tanjore H; Lee SB; Lebleu VS; Gattone VH Jr; Kalluri R. 2008. Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus. Dev Biol 313(2):584-93. [PubMed: 18082680]  [MGI Ref ID J:130822]

Li H; Oliver T; Jia W; He YW. 2006. Efficient dendritic cell priming of T lymphocytes depends on the extracellular matrix protein mindin. EMBO J 25(17):4097-107. [PubMed: 16917498]  [MGI Ref ID J:112875]

Liu S; Xu SW; Blumbach K; Eastwood M; Denton CP; Eckes B; Krieg T; Abraham DJ; Leask A. 2010. Expression of integrin beta1 by fibroblasts is required for tissue repair in vivo. J Cell Sci 123(Pt 21):3674-82. [PubMed: 20940256]  [MGI Ref ID J:182925]

Parapuram SK; Huh K; Liu S; Leask A. 2011. Integrin beta1 is necessary for the maintenance of corneal structural integrity. Invest Ophthalmol Vis Sci 52(11):7799-806. [PubMed: 21873663]  [MGI Ref ID J:189378]

Parkash J; Cimino I; Ferraris N; Casoni F; Wray S; Cappy H; Prevot V; Giacobini P. 2012. Suppression of beta1-integrin in gonadotropin-releasing hormone cells disrupts migration and axonal extension resulting in severe reproductive alterations. J Neurosci 32(47):16992-7002. [PubMed: 23175850]  [MGI Ref ID J:192809]

Pereira JP; An J; Xu Y; Huang Y; Cyster JG. 2009. Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nat Immunol 10(4):403-11. [PubMed: 19252491]  [MGI Ref ID J:147783]

Pozzi A; Jarad G; Moeckel GW; Coffa S; Zhang X; Gewin L; Eremina V; Hudson BG; Borza DB; Harris RC; Holzman LB; Phillips CL; Fassler R; Quaggin SE; Miner JH; Zent R. 2008. Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity. Dev Biol 316(2):288-301. [PubMed: 18328474]  [MGI Ref ID J:135414]

Raghavan S; Vaezi A; Fuchs E. 2003. A role for alphabeta1 integrins in focal adhesion function and polarized cytoskeletal dynamics. Dev Cell 5(3):415-27. [PubMed: 12967561]  [MGI Ref ID J:109020]

Simirskii VN; Wang Y; Duncan MK. 2007. Conditional deletion of beta1-integrin from the developing lens leads to loss of the lens epithelial phenotype. Dev Biol 306(2):658-68. [PubMed: 17493607]  [MGI Ref ID J:122566]

Stenzel D; Franco CA; Estrach S; Mettouchi A; Sauvaget D; Rosewell I; Schertel A; Armer H; Domogatskaya A; Rodin S; Tryggvason K; Collinson L; Sorokin L; Gerhardt H. 2011. Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo. EMBO Rep 12(11):1135-43. [PubMed: 21979816]  [MGI Ref ID J:178535]

Tanjore H; Zeisberg EM; Gerami-Naini B; Kalluri R. 2008. Beta1 integrin expression on endothelial cells is required for angiogenesis but not for vasculogenesis. Dev Dyn 237(1):75-82. [PubMed: 18058911]  [MGI Ref ID J:130422]

Turlo KA; Gallaher SD; Vora R; Laski FA; Iruela-Arispe ML. 2010. When cre-mediated recombination in mice does not result in protein loss. Genetics 186(3):959-67. [PubMed: 20813881]  [MGI Ref ID J:165707]

Turlo KA; Noel OD; Vora R; LaRussa M; Fassler R; Hall-Glenn F; Iruela-Arispe ML. 2012. An essential requirement for beta1 integrin in the assembly of extracellular matrix proteins within the vascular wall. Dev Biol 365(1):23-35. [PubMed: 22331032]  [MGI Ref ID J:184940]

Ulyanova T; Jiang Y; Padilla S; Nakamoto B; Papayannopoulou T. 2011. Combinatorial and distinct roles of alpha and alpha integrins in stress erythropoiesis in mice. Blood 117(3):975-85. [PubMed: 20956802]  [MGI Ref ID J:168417]

Wang QQ; Li H; Oliver T; Glogauer M; Guo J; He YW. 2008. Integrin beta1 regulates phagosome maturation in macrophages through Rac expression. J Immunol 180(4):2419-28. [PubMed: 18250451]  [MGI Ref ID J:131992]

Zhang X; Mernaugh G; Yang DH; Gewin L; Srichai MB; Harris RC; Iturregui JM; Nelson RD; Kohan DE; Abrahamson D; Fassler R; Yurchenco P; Pozzi A; Zent R. 2009. beta1 integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity. Development 136(19):3357-66. [PubMed: 19710172]  [MGI Ref ID J:153635]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375

Colony Maintenance

Breeding & Husbandry	Resulting chimeric animals were bred to C57BL/6J mice once before being made homozygous. Expected coat colors are: dark brown (almost black) it is suspected that they are a/a Tyr<c-ch>/Tyr<c-ch>.
Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

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 regarding Terms of Use

Contracts Administration

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

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

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