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| These Jag1dDSL, or Jag null, mutant mice may be useful in studies of Alagille Syndrome 1. | |||||||||||||||
- 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) 09-APR-13 Mating System Heterozygote x Wild-type (Female x Male) 09-APR-13 Species laboratory mouse Generation N11+F4 (18-JUN-12)
Generation DefinitionsDonating Investigator Tom Gridley, Maine Medical Center Research Institute Description
Mice that are heterozygous for the targeted mutation are viable, fertile, and normal in size. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis of homozygous embryos, aged embryonic day 10. Homozygotes have an embryonic lethal phenotype, with defective vasculature formation in the embryo and yolk sac and widespread hemorrhaging at embryonic day 10.5. Heterozygotes exhibit iris coloboma, irregular/off center pupils and corneal opacity.Development
A targeting vector containing a neo cassette was used to delete 5kb of sequence at the 5' end of the gene, which encodes the C-terminal part of the DSL domain. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The mice were backcrossed to C57BL/6J for 10 generations.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Facebase: models
View Facebase: models (58 strains)
010618 B6;129S-Jag1tm2Grid/J
Phenotype
Phenotype Information
- No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.
Alagille Syndrome 1; ALGS1
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Jagged 1; JAG1 (JAG1)
Tetralogy of Fallot; TOF (JAG1)
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Jag1tm1Grid/Jag1+
involves: 129S1/Sv * C57BL/6 * FVB
- vision/eye phenotype
- abnormal eye morphology
- eye phenotypes are described as fully penetrant on an 80% C57BL/6 genetic background and incompletely penetrant on a mixed background (MGI Ref ID J:54907)
Jag1tm1Grid/Jag1tm1Grid
involves: 129S1/Sv * C57BL/6 * FVB
- mortality/aging
- complete embryonic lethality during organogenesis
- embryogenesis phenotype
- abnormal vitelline vascular remodeling
- large blood vessels are absent from the yolk sacs (MGI Ref ID J:54907)
- pale yolk sac
- a pale yolk sac is seen at E10.5 (MGI Ref ID J:54907)
- cardiovascular system phenotype
- abnormal vascular development
- the vascular network in the forebrain of mutant embryos is not as well developed as in controls (MGI Ref ID J:54907)
- large blood vessels of the head have an abnormal appearance and a reduced diameter (MGI Ref ID J:54907)
- the primary vascular plexus of the yolk sac does not remodel into large blood vessels (MGI Ref ID J:54907)
- abnormal vitelline vascular remodeling
- large blood vessels are absent from the yolk sacs (MGI Ref ID J:54907)
- hemorrhage
- widespread, including embryonic and extraembryonic tissues observed at E10.5 (MGI Ref ID J:54907)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Vascular Defects
Developmental Biology Research
Embryonic Lethality (Homozygous)
Eye Defects
Internal/Organ Defects
vasculature
Sensorineural Research
Eye Defects
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Jag1tm1Grid | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Tom Gridley | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Jag1dDSL; Jag1del1; Jag1null; | ||
| Mutation Made By | Tom Gridley, Maine Medical Center Research Institute | ||
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| Gene Symbol and Name | Jag1, jagged 1 | ||
| Chromosome | 2 | ||
| Gene Common Name(s) | ABE2; AGS; AHD; AWS; CD339; Gsfabe2; HJ1; Headturner; Htu; JAGL1; Ozz; Serrate-1; gsf abnormal behavior 2; headturner; ozzy; | ||
| Molecular Note | A 5kb genomic fragment at the 5' end of the gene was replaced by a neomycin resistance cassette. These deleted sequences include coding regions for the C-terminal portion of the DSL domain. RT-PCR analysis demonstrated that no transcript was detectablein RNA isolated from E10 homozygous embryos, and Western blot analysis on extracts of E10.5 homozygous embryos confirmed that the protein was not expressed. [MGI Ref ID J:54907] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Jag1tm1Grid, Melt Curve Analysis
Jag1tm1Grid, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Xue Y; Gao X; Lindsell CE; Norton CR; Chang B; Hicks C; Gendron-Maguire M ; Rand EB ; Weinmaster G ; Gridley T. 1999. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1. Hum Mol Genet 8(5):723-30. [PubMed: 10196361] [MGI Ref ID J:54907]
Additional References
Jag1tm1Grid relatedBenedito R; Roca C; Sorensen I; Adams S; Gossler A; Fruttiger M; Adams RH. 2009. The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell 137(6):1124-35. [PubMed: 19524514] [MGI Ref ID J:157345]
Feng X; Krebs LT; Gridley T. 2010. Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion. Development 137(24):4191-9. [PubMed: 21068062] [MGI Ref ID J:166769]
Fernandez-Valdivia R; Takeuchi H; Samarghandi A; Lopez M; Leonardi J; Haltiwanger RS; Jafar-Nejad H. 2011. Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi. Development 138(10):1925-34. [PubMed: 21490058] [MGI Ref ID J:171432]
Guiu J; Shimizu R; D'Altri T; Fraser ST; Hatakeyama J; Bresnick EH; Kageyama R; Dzierzak E; Yamamoto M; Espinosa L; Bigas A. 2013. Hes repressors are essential regulators of hematopoietic stem cell development downstream of Notch signaling. J Exp Med 210(1):71-84. [PubMed: 23267012] [MGI Ref ID J:194596]
Kiernan AE; Ahituv N; Fuchs H; Balling R; Avraham KB; Steel KP; Hrabe de Angelis M. 2001. The Notch ligand Jagged1 is required for inner ear sensory development. Proc Natl Acad Sci U S A 98(7):3873-8. [PubMed: 11259677] [MGI Ref ID J:72108]
Kiernan AE; Li R; Hawes NL; Churchill GA; Gridley T. 2007. Genetic background modifies inner ear and eye phenotypes of jag1 heterozygous mice. Genetics 177(1):307-11. [PubMed: 17890364] [MGI Ref ID J:125211]
Kiernan AE; Xu J; Gridley T. 2006. The Notch ligand JAG1 is required for sensory progenitor development in the mammalian inner ear. PLoS Genet 2(1):e4. [PubMed: 16410827] [MGI Ref ID J:115783]
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; 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]
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]
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]
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]
Robert-Moreno A; Guiu J; Ruiz-Herguido C; Lopez ME; Ingles-Esteve J; Riera L; Tipping A; Enver T; Dzierzak E; Gridley T; Espinosa L; Bigas A. 2008. Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1. EMBO J 27(13):1886-95. [PubMed: 18528438] [MGI Ref ID J:137647]
Rodilla V; Villanueva A; Obrador-Hevia A; Robert-Moreno A; Fernandez-Majada V; Grilli A; Lopez-Bigas N; Bellora N; Alba MM; Torres F; Dunach M; Sanjuan X; Gonzalez S; Gridley T; Capella G; Bigas A; Espinosa L. 2009. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer. Proc Natl Acad Sci U S A 106(15):6315-20. [PubMed: 19325125] [MGI Ref ID J:147760]
Ryan MJ; Bales C; Nelson A; Gonzalez DM; Underkoffler L; Segalov M; Wilson-Rawls J; Cole SE; Moran JL; Russo P; Spinner NB; Kusumi K; Loomes KM. 2008. Bile duct proliferation in Jag1/fringe heterozygous mice identifies candidate modifiers of the Alagille syndrome hepatic phenotype. Hepatology 48(6):1989-97. [PubMed: 19026002] [MGI Ref ID J:152514]
Yen HY; Ting MC; Maxson RE. 2010. Jagged1 functions downstream of Twist1 in the specification of the coronal suture and the formation of a boundary between osteogenic and non-osteogenic cells. Dev Biol 347(2):258-70. [PubMed: 20727876] [MGI Ref ID J:166632]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as heterozygotes. Homozygotes are embryonic lethal due to hemorrhaging. Mating System Wild-type x Heterozygote (Female x Male) 09-APR-13 Heterozygote x Wild-type (Female x Male) 09-APR-13 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 Jag1tm1Grid
Price per Pair (US dollars $) Pair Genotype $296.00 Heterozygous for Jag1tm1Grid x Wild-type for Jag1tm1Grid $296.00 Wild-type for Jag1tm1Grid x Heterozygous for Jag1tm1Grid 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 Jag1tm1Grid
Price per Pair (US dollars $) Pair Genotype $384.80 Heterozygous for Jag1tm1Grid x Wild-type for Jag1tm1Grid $384.80 Wild-type for Jag1tm1Grid x Heterozygous for Jag1tm1Grid 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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|
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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 | ||
|---|---|---|
| Wild-type from the colony | ||
| 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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