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| This Notch2del1 hypomorphic mutant mouse strain may be useful in studies of kidney, eye, heart and vascular development. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
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. Mating System Wild-type x Heterozygote (Female x Male) 11-DEC-12 Mating System Heterozygote x Wild-type (Female x Male) 11-DEC-12 Species laboratory mouse Generation [N10p]+F4 (27-AUG-12)
Generation DefinitionsDonating Investigator Tom Gridley, Maine Medical Center Research Institute Description
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Due to alternative splicing, 2 in-frame gene products (mRNA) are detected by RT-PCR analysis of homozygous embryos. The mutant transcripts would produce proteins with one or two EGF repeats deleted. Levels of the mutant transcripts are similar to the wildtype transcript level. This targeted allele is a hypomorph. Homozygotes are neonatal lethal due to developmental defects in the kidney, heart and eye vasculature. Homozygous neonates exhibit hypoplastic kidneys, with vasculature lesions at the cortical surface, and lack mature glomeruli. Bilateral microphthalmia, with retrolenticular hyperplasia, is observed in homozygotes. At age embryonic day 11.5, some homozygous embryos exhibit delayed growth, pericardial effusion and widespread hemorrhaging. Homozygous embryos that survive past embryonic day 11.5 display myocardial hypoplasia, hemorrhaging and edema. By embryonic day 13.5, edema and hemorrhaging skin vessels is observed in homozygous embryos.Development
A targeting vector containing PGK-neo and HSV-tk cassettes was used to delete 0.4 kb of sequence, including most of the exon encoding the EGF repeat 14, the splice donor site, and 0.3 kb of intron sequence. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to C57BL/6J females and then backcrossed to C57BL/6J for 9 genertions. The mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the distribution colony.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Facebase: models
View Facebase: models (58 strains)
010525 B6.129S-Notch2tm3Grid/J
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 information may relate to a genetic background differing from this JAX® Mice strain.
Notch2tm1Grid/Notch2tm1Grid
involves: 129S1/Sv * C57BL/6J
- mortality/aging
- partial neonatal lethality
- incomplete penetrance; many animals die within the first 24 hours after birth (MGI Ref ID J:67157)
- partial prenatal lethality
- renal/urinary system phenotype
- abnormal kidney cortex morphology
- vascular lesions evident at the cortical surface (MGI Ref ID J:67157)
- abnormal podocyte morphology
- cells that expressed markers of podocyte differentiation were clumped together in the center of the glomerulus, and did not form the cup-shaped epithelial layer observed in the controls (MGI Ref ID J:67157)
- abnormal renal glomerulus morphology
- at E16.5, no morphologically normal glomeruli present (MGI Ref ID J:67157)
- frequently, the glomerulus appears as a disorganized clump of cells (MGI Ref ID J:67157)
- the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule (MGI Ref ID J:67157)
- abnormal ureteric bud morphology (MGI Ref ID J:67157)
- impaired branching involved in ureteric bud morphogenesis (MGI Ref ID J:67157)
- decreased kidney cell proliferation
- at E15.5, no proliferating cells were observed inside the abnormal glomeruli whereas these cells were detected in control mice (MGI Ref ID J:67157)
- increased kidney apoptosis
- at E15.5, an increased number of apoptotic cells was observed in the kidney of apoptotic cells in the kidney were observed (MGI Ref ID J:67157)
- kidney microaneurysm
- the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule (MGI Ref ID J:67157)
- small kidney
- at E16.5, kidneys were smaller than controls (MGI Ref ID J:67157)
- renal hypoplasia (MGI Ref ID J:67157)
- cardiovascular system phenotype
- abnormal glomerular capillary endothelium morphology
- few endothelial cells were present in the abnormal mutant glomeruli (MGI Ref ID J:67157)
- abnormal myocardial trabeculae morphology
- reduced myocardial trabeculation evident by E12.5 and thereafter (MGI Ref ID J:67157)
- heart hypoplasia
- in embryos surviving past E11.5, myocardial hypoplasia is evident, with hemorrhaging and edema (MGI Ref ID J:67157)
- hemorrhage
- 40% of embryos exhibited widespread hemorrhaging at E11.5; also evident in later embryonic stages (MGI Ref ID J:67157)
- kidney microaneurysm
- the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule (MGI Ref ID J:67157)
- pericardial effusion
- 40% of embryos exhibited pericardial effusion at E11.5 (MGI Ref ID J:67157)
- vision/eye phenotype
- abnormal eye morphology
- pronounced asymmetry of the eyes (MGI Ref ID J:67157)
- homeostasis/metabolism phenotype
- pericardial effusion
- 40% of embryos exhibited pericardial effusion at E11.5 (MGI Ref ID J:67157)
- skin edema
- 50% of embryos at E13.5 showed edema and hemorrhaging vessels near skin surface (MGI Ref ID J:67157)
- growth/size phenotype
- embryonic growth retardation
- by E11.5, 40% of embryos showed growth retardation (MGI Ref ID J:67157)
- liver/biliary system phenotype
- abnormal bile duct development
- bile duct epithelial cell differentiation defects occur (MGI Ref ID J:74574)
- muscle phenotype
- abnormal myocardial trabeculae morphology
- reduced myocardial trabeculation evident by E12.5 and thereafter (MGI Ref ID J:67157)
- embryogenesis phenotype
- embryonic growth retardation
- by E11.5, 40% of embryos showed growth retardation (MGI Ref ID J:67157)
- endocrine/exocrine gland phenotype
- abnormal bile duct development
- bile duct epithelial cell differentiation defects occur (MGI Ref ID J:74574)
- integument phenotype
- skin edema
- 50% of embryos at E13.5 showed edema and hemorrhaging vessels near skin surface (MGI Ref ID J:67157)
- cellular phenotype
- decreased kidney cell proliferation
- at E15.5, no proliferating cells were observed inside the abnormal glomeruli whereas these cells were detected in control mice (MGI Ref ID J:67157)
- increased kidney apoptosis
- at E15.5, an increased number of apoptotic cells was observed in the kidney of apoptotic cells in the kidney were observed (MGI Ref ID J:67157)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Vascular Defects
Developmental Biology Research
Eye Defects
Internal/Organ Defects
heart
heart: vasculature
kidney
vasculature
Perinatal Lethality
Homozygous
Internal/Organ Research
Heart Abnormalities
Kidney Defects
Sensorineural Research
Eye Defects
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Notch2tm1Grid | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Tom Gridley | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Notch2-; Notch2del1; | ||
| 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 | This is a hypomorphic allele. A neomycin resistance cassette replaced 0.4 kb of sequence, including part of the exon encoding EGF repeat 14, the splice donor site at the 3' end of this exon, and 0.3 kb of intron. mRNA species are detected in homozygousmutant embryos that appear to be the result of inframe splicing around the neomycin cassette. Proteins derived from these transcripts are predicted to have a deletion of one or two EGF repeats. [MGI Ref ID J:67157] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Notch2tm1Grid, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
McCright B; Gao X; Shen L; Lozier J; Lan Y; Maguire M; Herzlinger D; Weinmaster G; Jiang R; Gridley T. 2001. Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development 128(4):491-502. [PubMed: 11171333] [MGI Ref ID J:67157]
Additional References
Notch2tm1Grid relatedKrebs LT; Iwai N; Nonaka S; Welsh IC; Lan Y; Jiang R; Saijoh Y; O'Brien TP; Hamada H; Gridley T. 2003. Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev 17(10):1207-12. [PubMed: 12730124] [MGI Ref ID J:83358]
Loomes KM; Russo P; Ryan M; Nelson A; Underkoffler L; Glover C; Fu H; Gridley T; Kaestner KH; Oakey RJ. 2007. Bile duct proliferation in liver-specific Jag1 conditional knockout mice: effects of gene dosage. Hepatology 45(2):323-30. [PubMed: 17366661] [MGI Ref ID J:149131]
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]
McCright B; Lozier J; Gridley T. 2002. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency. Development 129(4):1075-82. [PubMed: 11861489] [MGI Ref ID J:74574]
Meyer-Bahlburg A; Andrews SF; Yu KO; Porcelli SA; Rawlings DJ. 2008. Characterization of a late transitional B cell population highly sensitive to BAFF-mediated homeostatic proliferation. J Exp Med 205(1):155-68. [PubMed: 18180309] [MGI Ref ID J:131142]
Nadeau JH. 2003. Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13(3):290-5. [PubMed: 12787792] [MGI Ref ID J:88012]
You Y; Myers RC; Freeberg L; Foote J; Kearney JF; Justement LB; Carter RH. 2011. Marginal zone B cells regulate antigen capture by marginal zone macrophages. J Immunol 186(4):2172-81. [PubMed: 21257969] [MGI Ref ID J:168986]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number FGB29
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes die within a day of birth. Mating System Wild-type x Heterozygote (Female x Male) 11-DEC-12 Heterozygote x Wild-type (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 $232.00 Female or Male Heterozygous for Notch2tm1Grid
Price per Pair (US dollars $) Pair Genotype $296.00 Heterozygous for Notch2tm1Grid x Wild-type for Notch2tm1Grid $296.00 Wild-type for Notch2tm1Grid x Heterozygous for Notch2tm1Grid 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 $301.60 Female or Male Heterozygous for Notch2tm1Grid
Price per Pair (US dollars $) Pair Genotype $384.80 Heterozygous for Notch2tm1Grid x Wild-type for Notch2tm1Grid $384.80 Wild-type for Notch2tm1Grid x Heterozygous for Notch2tm1Grid 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.
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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 | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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
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