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| These Notch2flox mutant mice may be useful in generating conditional mutations for studying the Notch pathway during development and embryogenesis. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Former Names B6.129S-Notch2tm3Grid/J (Changed: 28-APR-10 ) B6.129S1-Notch2tm3Grid/J (Changed: 28-APR-10 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 11-DEC-12 Species laboratory mouse Donating Investigator Tom Gridley, Maine Medical Center Research Institute 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 these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissue(s).When bred to a strain with early embryonic Cre recombinase expression (see Stock No. 003755 for example), this mutant mouse strain may be useful in studies of the Notch pathway during development.
When bred to a strain expressing Cre recombinase in embryos, in particular, cardiac neural crest cells (see Stock No. 005549 for example), this mutant mouse strain may be useful in studies of vascular smooth muscle development and the cardiovascular defects associated with Alagille syndrome.
When bred to a strain expressing Cre recombinase in liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of bile duct morphogenesis.
When bred to a strain expressing Cre recombinase in vascular smooth muscle cells (see Stock No. 004746 for example), this mutant mouse strain may be useful in studies of vascular smooth muscle development.
When bred to a strain expressing Cre recombinase in the olfactory epithelium and developing head structures (see Stock No. 006084 for example), this mutant mouse strain may be useful in studies of neuroglial cell maintenance.
Development
A loxP site flanked targeting vector containing a FRT-site flanked PGK-Neo selection cassette was utilized in the construction of this mutant. This selection cassette was inserted upstream of exon 3 of the targeted gene, and another loxP site was inserted downstream of exon 3. This construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting male chimeric animals were crossed to C57BL/6J females. The mice were bred to 129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J mice (Stock No. 003946) to remove the FRT-site flanked PGK-neo cassette. Mice that retained the loxP site flanked exon 3 were then bred to C57BL/6 mice for 10 generations and to remove the Flp recombinase allele. Heterozygotes were crossed to generate homozygotes.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Facebase: models
View Facebase: models (58 strains)
010620 B6.129S1-Notch2tm1Grid/J
Additional Web Information
Introduction to Cre-lox technology
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Alagille Syndrome 2; ALGS2 (NOTCH2)
Hajdu-Cheney Syndrome; HJCYS (NOTCH2)
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.Notch2tm3Grid/Notch2tm3.1Grid Tg(Alb-cre)21Mgn/0
involves: 129S1/Sv * C57BL/6 * DBA (conditional)
- liver/biliary system phenotype
- abnormal bile duct morphology
- by P7 few bile ducts are present (MGI Ref ID J:133171)
- focal hepatic necrosis (MGI Ref ID J:133171)
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype
- blood urea nitrogen levels are normal (MGI Ref ID J:133171)
- growth/size phenotype
- decreased body size (MGI Ref ID J:133171)
- endocrine/exocrine gland phenotype
- abnormal bile duct morphology
- by P7 few bile ducts are present (MGI Ref ID J:133171)
Notch2tm3Grid/Notch2tm3.1Grid Tg(Tagln-cre)1Her/?
involves: 129 * C57BL/6 (conditional)
- mortality/aging
- partial postnatal lethality
- there is a 50% mortality rate between birth and weaning (MGI Ref ID J:132939)
- cardiovascular system phenotype
- abnormal blood flow velocity
- mean aortic velocity in one month old mice is 1.74 m/s which is significantly faster than the mean velocity of 0.93 m/s for controls (MGI Ref ID J:132939)
- mean pulmonary velocity in one month old mice is 1.9 m/s which is significantly faster than the mean velocity of 1.5 m/s for controls (MGI Ref ID J:132939)
- aorta stenosis
- aorta diameters of all E18.5 embryos and newborns are decreased compared to wild-type mice (MGI Ref ID J:132939)
- pulmonary artery stenosis
- pulmonary arteries of E18.5 embryos and newborns are significantly smaller (MGI Ref ID J:132939)
- homeostasis/metabolism phenotype
- cyanosis
- is observed in neonates (MGI Ref ID J:132939)
Notch2tm3Grid/Notch2tm3.1Grid Pax3tm1(cre)Joe/Pax3+
involves: 129 * C57BL/6 (conditional)
- mortality/aging
- partial postnatal lethality
- there is a 50% mortality rate between birth and weaning (MGI Ref ID J:132939)
- cardiovascular system phenotype
- abnormal vascular smooth muscle morphology
- smooth muscle cell proliferation is reduced to 9% in E16.5 embryos compared to 22.5% of wild-type embryos (MGI Ref ID J:132939)
- aorta stenosis
- pulmonary artery stenosis
- pulmonary arteries of E18.5 embryos and newborns are significantly smaller (MGI Ref ID J:132939)
- supravalvar pulmonary trunk stenosis
- the mean inner diameter of the pulmonary trunk is 1.22 mm compared to 1.56 mm for age-matched controls (MGI Ref ID J:132939)
- craniofacial phenotype
- abnormal tooth morphology
- dental malformations inhibit the ability of mice to feed postnatally (MGI Ref ID J:132939)
- growth/size phenotype
- decreased body weight
- by one week of age, mice weigh significantly less than control littermates (MGI Ref ID J:132939)
- homeostasis/metabolism phenotype
- cyanosis
- a mild cyanotic appearance is observed in neonates (MGI Ref ID J:132939)
- muscle phenotype
- abnormal vascular smooth muscle morphology
- smooth muscle cell proliferation is reduced to 9% in E16.5 embryos compared to 22.5% of wild-type embryos (MGI Ref ID J:132939)
Notch2tm3Grid/Notch2tm3Grid Foxg1tm1(cre)Skm/Foxg1+
involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6 (conditional)
- mortality/aging
- premature death
- growth/size phenotype
- decreased body weight
- nervous system phenotype
- abnormal nervous system physiology
- lower Glutathione S-transferase activity in mutant olfactory epithelia (MGI Ref ID J:130929)
- increased neuron apoptosis
- neuron degeneration
- abnormal sensory neuron morphology
- disorganized olfactory sensory neurons (MGI Ref ID J:130929)
- increased neuronal precursor cell number
- increased olfactory neuronal progenitors in the neuronal and apical layer in adults mutants (MGI Ref ID J:130929)
- small pituitary gland
- significantly smaller pituitary in size (MGI Ref ID J:130929)
- taste/olfaction phenotype
- abnormal olfactory epithelium morphology
- disrupted relatively uniform spacing of sustentacular nuclei (MGI Ref ID J:130929)
- some areas significantly disrupted and thinner, other areas appear relatively normal (MGI Ref ID J:130929)
- smaller and more irregularly shaped sustentacular nuclei (MGI Ref ID J:130929)
- gaps and a reduction in the number of dendritic tufts at the apical surface (MGI Ref ID J:130929)
- cellular phenotype
- increased apoptosis
- increased TUNEL-positive cells in the apical layer of the olfactory epithelium (0.3 cells/mm vs. 0/mm) (MGI Ref ID J:130929)
- increased neuronal precursor cell number
- increased olfactory neuronal progenitors in the neuronal and apical layer in adults mutants (MGI Ref ID J:130929)
- endocrine/exocrine gland phenotype
- small pituitary gland
- significantly smaller pituitary in size (MGI Ref ID J:130929)
- respiratory system phenotype
- abnormal olfactory epithelium morphology
- disrupted relatively uniform spacing of sustentacular nuclei (MGI Ref ID J:130929)
- some areas significantly disrupted and thinner, other areas appear relatively normal (MGI Ref ID J:130929)
- smaller and more irregularly shaped sustentacular nuclei (MGI Ref ID J:130929)
- gaps and a reduction in the number of dendritic tufts at the apical surface (MGI Ref ID J:130929)
- craniofacial phenotype
- abnormal olfactory epithelium morphology
- disrupted relatively uniform spacing of sustentacular nuclei (MGI Ref ID J:130929)
- some areas significantly disrupted and thinner, other areas appear relatively normal (MGI Ref ID J:130929)
- smaller and more irregularly shaped sustentacular nuclei (MGI Ref ID J:130929)
- gaps and a reduction in the number of dendritic tufts at the apical surface (MGI Ref ID J:130929)
This mouse can be used to support research in many areas including:
Research Tools
Cre-lox System
loxP-flanked Sequences
Developmental Biology Research
Cre-lox System
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Notch2tm3Grid | ||
|---|---|---|---|
| Allele Name | targeted mutation 3, Tom Gridley | ||
| Allele Type | Targeted (Floxed/Frt) | ||
| Common Name(s) | N2f; N2flox; Notch2Fl; Notch2flox; | ||
| Mutation Made By | Tom Gridley, Maine Medical Center Research Institute | ||
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| Gene Symbol and Name | Notch2, notch 2 | ||
| Chromosome | 3 | ||
| Gene Common Name(s) | AGS2; AI853703; HJCYS; Motch B; N2; expressed sequence AI853703; hN2; | ||
| Molecular Note | loxP sites were inserted to flank exon 3. [MGI Ref ID J:105278] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Notch2tm3Grid, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
McCright B; Lozier J; Gridley T. 2006. Generation of new Notch2 mutant alleles. Genesis 44(1):29-33. [PubMed: 16397869] [MGI Ref ID J:105278]
Additional References
Notch2tm3Grid relatedBoyle 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]
Germar K; Dose M; Konstantinou T; Zhang J; Wang H; Lobry C; Arnett KL; Blacklow SC; Aifantis I; Aster JC; Gounari F. 2011. T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling. Proc Natl Acad Sci U S A 108(50):20060-5. [PubMed: 22109558] [MGI Ref ID J:180443]
Hashimoto-Torii K; Torii M; Sarkisian MR; Bartley CM; Shen J; Radtke F; Gridley T; Sestan N; Rakic P. 2008. Interaction between Reelin and Notch signaling regulates neuronal migration in the cerebral cortex. Neuron 60(2):273-84. [PubMed: 18957219] [MGI Ref ID J:144065]
Hatton BA; Villavicencio EH; Pritchard J; LeBlanc M; Hansen S; Ulrich M; Ditzler S; Pullar B; Stroud MR; Olson JM. 2010. Notch signaling is not essential in sonic hedgehog-activated medulloblastoma. Oncogene 29(26):3865-72. [PubMed: 20440271] [MGI Ref ID J:168168]
Helbig C; Gentek R; Backer RA; de Souza Y; Derks IA; Eldering E; Wagner K; Jankovic D; Gridley T; Moerland PD; Flavell RA; Amsen D. 2012. Notch controls the magnitude of T helper cell responses by promoting cellular longevity. Proc Natl Acad Sci U S A 109(23):9041-6. [PubMed: 22615412] [MGI Ref ID J:184840]
Hunkapiller NM; Gasperowicz M; Kapidzic M; Plaks V; Maltepe E; Kitajewski J; Cross JC; Fisher SJ. 2011. A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. Development 138(14):2987-98. [PubMed: 21693515] [MGI Ref ID J:173527]
Lewis KL; Caton ML; Bogunovic M; Greter M; Grajkowska LT; Ng D; Klinakis A; Charo IF; Jung S; Gommerman JL; Ivanov II; Liu K; Merad M; Reizis B. 2011. Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity 35(5):780-91. [PubMed: 22018469] [MGI Ref ID J:178710]
Lozier J; McCright B; Gridley T. 2008. Notch signaling regulates bile duct morphogenesis in mice. PLoS ONE 3(3):e1851. [PubMed: 18365007] [MGI Ref ID J:133171]
Massa F; Garbay S; Bouvier R; Sugitani Y; Noda T; Gubler MC; Heidet L; Pontoglio M; Fischer E. 2013. Hepatocyte nuclear factor 1beta controls nephron tubular development. Development 140(4):886-96. [PubMed: 23362349] [MGI Ref ID J:194050]
Morimoto M; Nishinakamura R; Saga Y; Kopan R. 2012. Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells. Development 139(23):4365-73. [PubMed: 23132245] [MGI Ref ID J:190886]
Rodriguez S; Sickles HM; Deleonardis C; Alcaraz A; Gridley T; Lin DM. 2008. Notch2 is required for maintaining sustentacular cell function in the adult mouse main olfactory epithelium. Dev Biol 314(1):40-58. [PubMed: 18155189] [MGI Ref ID J:130929]
Saravanamuthu SS; Le TT; Gao CY; Cojocaru RI; Pandiyan P; Liu C; Zhang J; Zelenka PS; Brown NL. 2012. Conditional ablation of the Notch2 receptor in the ocular lens. Dev Biol 362(2):219-29. [PubMed: 22173065] [MGI Ref ID J:180791]
Surendran K; Boyle S; Barak H; Kim M; Stomberski C; McCright B; Kopan R. 2010. The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. Dev Biol 337(2):386-95. [PubMed: 19914235] [MGI Ref ID J:157258]
Tu X; Chen J; Lim J; Karner CM; Lee SY; Heisig J; Wiese C; Surendran K; Kopan R; Gessler M; Long F. 2012. Physiological notch signaling maintains bone homeostasis via RBPjk and Hey upstream of NFATc1. PLoS Genet 8(3):e1002577. [PubMed: 22457635] [MGI Ref ID J:183534]
Varadkar P; Kraman M; Despres D; Ma G; Lozier J; McCright B. 2008. Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells. Dev Dyn 237(4):1144-52. [PubMed: 18330927] [MGI Ref ID J:132939]
Zanotti S; Canalis E. 2013. Notch suppresses nuclear factor of activated T cells (NFAT) transactivation and Nfatc1 expression in chondrocytes. Endocrinology 154(2):762-72. [PubMed: 23264614] [MGI Ref ID J:194597]
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) 11-DEC-12 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $177.00 Female or Male Homozygous for Notch2tm3Grid
Price per Pair (US dollars $) Pair Genotype $354.00 Homozygous for Notch2tm3Grid x Homozygous for Notch2tm3Grid Standard Supply
Repository-Live. Repository-Live represents 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. Repository-live orders are treated 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 |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $230.10 Female or Male Homozygous for Notch2tm3Grid
Price per Pair (US dollars $) Pair Genotype $460.20 Homozygous for Notch2tm3Grid x Homozygous for Notch2tm3Grid Standard Supply
Repository-Live. Repository-Live represents 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. Repository-live orders are treated 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.
|
|
|
Standard Supply
Repository-Live. Repository-Live represents 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. Repository-live orders are treated 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.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| 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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