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| When used in conjunction with a Cre recombinase-expressing strain, these RosaN1-IC (or RosaNotch) mutant mice may be useful in generating conditional mutations for studying the effects of Notch pathway activation. | |||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
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) 12-NOV-08 Species laboratory mouse Generation F?+F7 (01-DEC-11)
Generation DefinitionsDonating Investigator Douglas Melton, Harvard University Description
These mice contain a sequence encoding an intracellular portion of the mouse Notch1 gene (amino acids 1749-2293), but lacking the c-terminal PEST domain, and Green Fluorescent Protein, GFP, inserted into the GT(ROSA)26Sor locus. Expression of the Notch1 fragment and GFP is blocked by a loxP-flanked STOP fragment placed between the coding sequence and the GT(ROSA)26Sor promoter. The GFP expression is localized to the nucleus by an IRES sequence. The truncated cytoplasmic fragment encoded by the Notch1 sequence causes constitutive signaling activity. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants for studying the effects of Notch pathway activation. Homozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.For example, when crossed to a strain expressing a tamoxifen inducible Cre recombinase in all cells that express Shh (see Stock No. 005623), this mutant mouse strain may be useful in studies of Notch signaling.
When crossed to a strain expressing a tamoxifen inducible Cre recombinase in all cells that express Neurog3 such as spermatogonia and pancreatic islets cells (see Stock No. 008119), this mutant mouse strain may be useful in studies of Notch signaling.
When bred to a strain expression interferon inducible Cre recombinase in liver and lymphocytes (see Stock No. 003556 for example), this mutant mouse strain may be useful in studies of Notch signaling in lymphocyte development.
Development
A targeting vector containing a loxP- flanked neo-STOP cassette, mouse Notch1 sequence encoding amino acids 1749-2293 and GFP was inserted into the GT(ROSA)26Sor locus. The construct was introduced into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into receipient blastocysts. Resulting chimeric male animals were crossed to C57BL/6 females. The mice were then crossed to C57BL/6J for an unknown number of generations and maintained on the outbred ICR background.
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Gt(ROSA)26Sor
View Strains carrying other alleles of Gt(ROSA)26Sor (104 strains)
Additional Web Information
Introduction to Cre-lox technology
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Gt(ROSA)26Sortm1(Notch1)Dam/Gt(ROSA)26Sortm1(Notch1)Dam
involves: 129S4/SvJae * C57BL/6
- normal phenotype
- no abnormal phenotype detected
- mice are healthy and fertile (MGI Ref ID J:86975)
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Gt(ROSA)26Sortm1(Notch1)Dam/Gt(ROSA)26Sor+ Tg(Mx1-cre)1Cgn/0
involves: 129S4/SvJaeSor * C57BL/6 * CBA (conditional)
- mortality/aging
- premature death
- mutant bone marrow transplanted chimeras survive to 26 days after pI-pC treatment (MGI Ref ID J:167000)
- tumorigenesis
- leukemia
- hematopoietic system phenotype
- decreased B cell number
- decreased B220+ B cell numbers in mutant bone marrow transplanted chimeras (MGI Ref ID J:167000)
- enlarged spleen
- severe splenomegaly in mutant bone marrow transplanted chimeras (MGI Ref ID J:167000)
- increased leukocyte cell number
- increased WBC counts in mutant bone marrow transplanted chimeras (MGI Ref ID J:167000)
- immune system phenotype
- decreased B cell number
- decreased B220+ B cell numbers in mutant bone marrow transplanted chimeras (MGI Ref ID J:167000)
- enlarged spleen
- severe splenomegaly in mutant bone marrow transplanted chimeras (MGI Ref ID J:167000)
- increased leukocyte cell number
- increased WBC counts in mutant bone marrow transplanted chimeras (MGI Ref ID J:167000)
Gt(ROSA)26Sortm1(Notch1)Dam/Gt(ROSA)26Sor+ Tg(Neurog3-cre/Esr1*)1Dam/0
involves: 129S4/SvJae * C57BL/6 * CBA (conditional)
- mortality/aging
- complete embryonic lethality during organogenesis
- unable to recover any viable embryos after E13.5 (MGI Ref ID J:86975)
- endocrine/exocrine gland phenotype
- absent pancreatic alpha cells
- pancreas shows absence of glucagon+ alpha cells at E13.5 (MGI Ref ID J:86975)
Gt(ROSA)26Sortm1(Notch1)Dam/Gt(ROSA)26Sor+ Shhtm2(cre/ERT2)Cjt/Shh+
involves: 129S4/SvJaeSor * 129S6/SvEvTac (conditional)
- vision/eye phenotype
- *normal* vision/eye phenotype
- retina size is normal (MGI Ref ID J:118372)
This mouse can be used to support research in many areas including:
Cell Biology Research
Signal Transduction
Research Tools
Cre-lox System
loxP-flanked Sequences
Developmental Biology Research
Cre-lox System
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: Cre-lox System
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Gt(ROSA)26Sortm1(Notch1)Dam | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Douglas A Melton | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Lox-stop-Lox-RosaNICD-ires-GFP; R-NICD; R26NotchIC; R26N1ICD; ROSA-NICD; Rosa-NotchIC-IRES-GFP; Rosa26NIC; Rosa26NotchIC-IRES-GFP; RosaN1-IC; RosaNICD; RosaNotch; | ||
| Mutation Made By | Douglas Melton, Harvard University | ||
| Strain of Origin | 129S4/SvJaeSor | ||
| ES Cell Line Name | AK7 | ||
| ES Cell Line Strain | 129S4/SvJaeSor | ||
| Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | AV258896; Gtrgeo26; Gtrosa26; R26; ROSA26; beta geo; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26; | ||
| Molecular Note | A targeting vector containing a floxed neo cassette followed by a mouse Notch1 sequence fragment and GFP was inserted at the endogenous locus. Excision of the floxed neo cassette leads to the expression of the Notch1 sequence encoding an intracellular portion of NOTCH1 (amino acids 1749-2293), but lacking the c-terminal PEST domain. IRES preceded the sequence encoding the nuclear-localized enhanced GFP. [MGI Ref ID J:86975] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Gt(ROSA)26Sortm1(Notch1)Dam, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Murtaugh LC; Stanger BZ; Kwan KM; Melton DA. 2003. Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci U S A 100(25):14920-5. [PubMed: 14657333] [MGI Ref ID J:86975]
Additional References
Gt(ROSA)26Sortm1(Notch1)Dam relatedBasch ML; Ohyama T; Segil N; Groves AK. 2011. Canonical Notch Signaling Is Not Necessary for Prosensory Induction in the Mouse Cochlea: Insights from a Conditional Mutant of RBPj{kappa}. J Neurosci 31(22):8046-58. [PubMed: 21632926] [MGI Ref ID J:173382]
Blanpain C; Lowry WE; Pasolli HA; Fuchs E. 2006. Canonical notch signaling functions as a commitment switch in the epidermal lineage. Genes Dev 20(21):3022-35. [PubMed: 17079689] [MGI Ref ID J:114702]
Boyle SC; Kim M; Valerius MT; McMahon AP; Kopan R. 2011. Notch pathway activation can replace the requirement for Wnt4 and Wnt9b in mesenchymal-to-epithelial transition of nephron stem cells. Development 138(19):4245-54. [PubMed: 21852398] [MGI Ref ID J:176046]
Cheng HT; Kim M; Valerius MT; Surendran K; Schuster-Gossler K; Gossler A; McMahon AP; Kopan R. 2007. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development 134(4):801-11. [PubMed: 17229764] [MGI Ref ID J:119907]
Copeland JN; Feng Y; Neradugomma NK; Fields PE; Vivian JL. 2011. Notch signaling regulates remodeling and vessel diameter in the extraembryonic yolk sac. BMC Dev Biol 11:12. [PubMed: 21352545] [MGI Ref ID J:169692]
De La O JP; Emerson LL; Goodman JL; Froebe SC; Illum BE; Curtis AB; Murtaugh LC. 2008. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc Natl Acad Sci U S A 105(48):18907-12. [PubMed: 19028876] [MGI Ref ID J:142188]
Dong Y; Jesse AM; Kohn A; Gunnell LM; Honjo T; Zuscik MJ; O'Keefe RJ; Hilton MJ. 2010. RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development. Development 137(9):1461-71. [PubMed: 20335360] [MGI Ref ID J:159860]
Feller J; Schneider A; Schuster-Gossler K; Gossler A. 2008. Noncyclic Notch activity in the presomitic mesoderm demonstrates uncoupling of somite compartmentalization and boundary formation. Genes Dev 22(16):2166-71. [PubMed: 18708576] [MGI Ref ID J:138982]
Fre S; Huyghe M; Mourikis P; Robine S; Louvard D; Artavanis-Tsakonas S. 2005. Notch signals control the fate of immature progenitor cells in the intestine. Nature 435(7044):964-8. [PubMed: 15959516] [MGI Ref ID J:99364]
Fre S; Pallavi SK; Huyghe M; Lae M; Janssen KP; Robine S; Artavanis-Tsakonas S; Louvard D. 2009. Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine. Proc Natl Acad Sci U S A 106(15):6309-14. [PubMed: 19251639] [MGI Ref ID J:147579]
Goldberg LB; Aujla PK; Raetzman LT. 2011. Persistent expression of activated Notch inhibits corticotrope and melanotrope differentiation and results in dysfunction of the HPA axis. Dev Biol 358(1):23-32. [PubMed: 21781958] [MGI Ref ID J:176609]
Greenwood AL; Li S; Jones K; Melton DA. 2007. Notch signaling reveals developmental plasticity of Pax4(+) pancreatic endocrine progenitors and shunts them to a duct fate. Mech Dev 124(2):97-107. [PubMed: 17196797] [MGI Ref ID J:119944]
Guseh JS; Bores SA; Stanger BZ; Zhou Q; Anderson WJ; Melton DA; Rajagopal J. 2009. Notch signaling promotes airway mucous metaplasia and inhibits alveolar development. Development 136(10):1751-9. [PubMed: 19369400] [MGI Ref ID J:148016]
Hartman BH; Reh TA; Bermingham-McDonogh O. 2010. Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear. Proc Natl Acad Sci U S A 107(36):15792-7. [PubMed: 20798046] [MGI Ref ID J:164376]
Iulianella A; Sharma M; Vanden Heuvel GB; Trainor PA. 2009. Cux2 functions downstream of Notch signaling to regulate dorsal interneuron formation in the spinal cord. Development 136(14):2329-34. [PubMed: 19542352] [MGI Ref ID J:150348]
Jadhav AP; Cho SH; Cepko CL. 2006. Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property. Proc Natl Acad Sci U S A 103(50):18998-9003. [PubMed: 17148603] [MGI Ref ID J:118372]
Jayasena CS; Ohyama T; Segil N; Groves AK. 2008. Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode. Development 135(13):2251-61. [PubMed: 18495817] [MGI Ref ID J:137096]
Jeong HW; Jeon US; Koo BK; Kim WY; Im SK; Shin J; Cho Y; Kim J; Kong YY. 2009. Inactivation of Notch signaling in the renal collecting duct causes nephrogenic diabetes insipidus in mice. J Clin Invest 119(11):3290-300. [PubMed: 19855135] [MGI Ref ID J:154589]
Kim TH; Shivdasani RA. 2011. Notch signaling in stomach epithelial stem cell homeostasis. J Exp Med 208(4):677-88. [PubMed: 21402740] [MGI Ref ID J:176833]
Kim YW; Koo BK; Jeong HW; Yoon MJ; Song R; Shin J; Jeong DC; Kim SH; Kong YY. 2008. Defective Notch activation in microenvironment leads to myeloproliferative disease. Blood 112(12):4628-38. [PubMed: 18818392] [MGI Ref ID J:143346]
Kopinke D; Brailsford M; Shea JE; Leavitt R; Scaife CL; Murtaugh LC. 2011. Lineage tracing reveals the dynamic contribution of Hes1+ cells to the developing and adult pancreas. Development 138(3):431-41. [PubMed: 21205788] [MGI Ref ID J:169830]
Kwon C; Cheng P; King IN; Andersen P; Shenje L; Nigam V; Srivastava D. 2011. Notch post-translationally regulates beta-catenin protein in stem and progenitor cells. Nat Cell Biol 13(10):1244-51. [PubMed: 21841793] [MGI Ref ID J:176965]
Liu Z; Obenauf AC; Speicher MR; Kopan R. 2009. Rapid identification of homologous recombinants and determination of gene copy number with reference/query pyrosequencing (RQPS). Genome Res 19(11):2081-9. [PubMed: 19797679] [MGI Ref ID J:172930]
Luna-Zurita L; Prados B; Grego-Bessa J; Luxan G; del Monte G; Benguria A; Adams RH; Perez-Pomares JM; de la Pompa JL. 2010. Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation. J Clin Invest 120(10):3493-507. [PubMed: 20890042] [MGI Ref ID J:165329]
Magenheim J; Klein AM; Stanger BZ; Ashery-Padan R; Sosa-Pineda B; Gu G; Dor Y. 2011. Ngn3(+) endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium. Dev Biol 359(1):26-36. [PubMed: 21888903] [MGI Ref ID J:178171]
Mead TJ; Yutzey KE. 2009. Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development. Proc Natl Acad Sci U S A 106(34):14420-5. [PubMed: 19590010] [MGI Ref ID J:151888]
Mead TJ; Yutzey KE. 2012. Notch pathway regulation of neural crest cell development in vivo. Dev Dyn 241(2):376-89. [PubMed: 22275227] [MGI Ref ID J:179882]
Nelson BR; Ueki Y; Reardon S; Karl MO; Georgi S; Hartman BH; Lamba DA; Reh TA. 2011. Genome-wide analysis of Muller glial differentiation reveals a requirement for Notch signaling in postmitotic cells to maintain the glial fate. PLoS One 6(8):e22817. [PubMed: 21829655] [MGI Ref ID J:177592]
Pan W; Jin Y; Stanger B; Kiernan AE. 2010. Notch signaling is required for the generation of hair cells and supporting cells in the mammalian inner ear. Proc Natl Acad Sci U S A 107(36):15798-803. [PubMed: 20733081] [MGI Ref ID J:164383]
Rentschler S; Harris BS; Kuznekoff L; Jain R; Manderfield L; Lu MM; Morley GE; Patel VV; Epstein JA. 2011. Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways. J Clin Invest 121(2):525-33. [PubMed: 21266778] [MGI Ref ID J:171825]
Rock JR; Gao X; Xue Y; Randell SH; Kong YY; Hogan BL. 2011. Notch-dependent differentiation of adult airway basal stem cells. Cell Stem Cell 8(6):639-48. [PubMed: 21624809] [MGI Ref ID J:174231]
Rowan S; Conley KW; Le TT; Donner AL; Maas RL; Brown NL. 2008. Notch signaling regulates growth and differentiation in the mammalian lens. Dev Biol 321(1):111-22. [PubMed: 18588871] [MGI Ref ID J:138714]
Schaffer AE; Freude KK; Nelson SB; Sander M. 2010. Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors. Dev Cell 18(6):1022-9. [PubMed: 20627083] [MGI Ref ID J:163847]
Sorensen I; Adams RH; Gossler A. 2009. DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries. Blood 113(22):5680-8. [PubMed: 19144989] [MGI Ref ID J:148902]
Sparks EE; Perrien DS; Huppert KA; Peterson TE; Huppert SS. 2011. Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice. Dis Model Mech 4(3):359-67. [PubMed: 21282722] [MGI Ref ID J:171764]
Stanger BZ; Datar R; Murtaugh LC; Melton DA. 2005. Direct regulation of intestinal fate by Notch. Proc Natl Acad Sci U S A 102(35):12443-8. [PubMed: 16107537] [MGI Ref ID J:101154]
Suliman S; Tan J; Xu K; Kousis PC; Kowalski PE; Chang G; Egan SE; Guidos C. 2011. Notch3 is dispensable for thymocyte beta-selection and Notch1-induced T cell leukemogenesis. PLoS One 6(9):e24937. [PubMed: 21931869] [MGI Ref ID J:177688]
Tang H; Brennan J; Karl J; Hamada Y; Raetzman L; Capel B. 2008. Notch signaling maintains Leydig progenitor cells in the mouse testis. Development 135(22):3745-53. [PubMed: 18927153] [MGI Ref ID J:143587]
Vandussen KL; Carulli AJ; Keeley TM; Patel SR; Puthoff BJ; Magness ST; Tran IT; Maillard I; Siebel C; Kolterud A; Grosse AS; Gumucio DL; Ernst SA; Tsai YH; Dempsey PJ; Samuelson LC. 2012. Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells. Development 139(3):488-97. [PubMed: 22190634] [MGI Ref ID J:179656]
Wendorff AA; Koch U; Wunderlich FT; Wirth S; Dubey C; Bruning JC; MacDonald HR; Radtke F. 2010. Hes1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation. Immunity 33(5):671-84. [PubMed: 21093323] [MGI Ref ID J:167000]
Wu X; Xu K; Zhang L; Deng Y; Lee P; Shapiro E; Monaco M; Makarenkova HP; Li J; Lepor H; Grishina I. 2011. Differentiation of the ductal epithelium and smooth muscle in the prostate gland are regulated by the Notch/PTEN-dependent mechanism. Dev Biol 356(2):337-49. [PubMed: 21624358] [MGI Ref ID J:175387]
Yoon KJ; Koo BK; Im SK; Jeong HW; Ghim J; Kwon MC; Moon JS; Miyata T; Kong YY. 2008. Mind bomb 1-expressing intermediate progenitors generate notch signaling to maintain radial glial cells. Neuron 58(4):519-31. [PubMed: 18498734] [MGI Ref ID J:145294]
Zanotti S; Smerdel-Ramoya A; Stadmeyer L; Durant D; Radtke F; Canalis E. 2008. Notch inhibits osteoblast differentiation and causes osteopenia. Endocrinology 149(8):3890-9. [PubMed: 18420737] [MGI Ref ID J:138080]
Zong Y; Panikkar A; Xu J; Antoniou A; Raynaud P; Lemaigre F; Stanger BZ. 2009. Notch signaling controls liver development by regulating biliary differentiation. Development 136(10):1727-39. [PubMed: 19369401] [MGI Ref ID J:148015]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as homozygotes. Mating System Homozygote x Homozygote (Female x Male) 12-NOV-08 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $172.00 Female or Male Homozygous for Gt(ROSA)26Sortm1(Notch1)Dam
Pairs /Price (US dollars $) Pair Genotype $344.00 Homozygous for Gt(ROSA)26Sortm1(Notch1)Dam x Homozygous for Gt(ROSA)26Sortm1(Notch1)Dam Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $223.60 Female or Male Homozygous for Gt(ROSA)26Sortm1(Notch1)Dam
Pairs /Price (US dollars $) Pair Genotype $447.20 Homozygous for Gt(ROSA)26Sortm1(Notch1)Dam x Homozygous for Gt(ROSA)26Sortm1(Notch1)Dam Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| 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.Ordering Information
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