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| Homozygous Jag2deltaDSL mutant mice exhibit syndactyly and craniofacial defects that cause perinatal lethality. Heterozygotes have abnormal inner ear morphology. This mutant mouse strain may be useful in studies of craniofacial, limb and inner ear development. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
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. Species laboratory mouse Generation N10pN1
Generation DefinitionsDonating Investigator Tom Gridley, Maine Medical Center Research Institute Description
Mice that are homozygous for this targeted mutation have a perinatal lethal phenotype, dying shortly after birth due to craniofacial defects (cleft palate, due to fusion of unelevated palatal shelves with the tongue). Embryos homozygous for the mutation and aged embryonic day 10.5-11.5, display a hyperplastic thick apical ectodermal ridge of the limb buds. Homozygous neonates have bilateral cleft of the secondary palate and syndactyly (fused digits) of both forelimbs and hindlimbs, although the hindlimbs are more affected. The number of inner ear hair cells is increased in mutants. Histological analysis reveals an increased number of inner ear hair cells and disorganized stereocilia bundles in mutants. Homozygotes exhibit abnormal thymic morphology and decreased gamma-delta T cell number. Heterozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Heterozygotes have abnormal inner ear morphology (increased number of hair cells).Development
A targeting vector containing a PGK-neo cassette was used to disrupt 5.0kb of sequence containing the exons which encode the DSL domain and half of the first EGF repeat. 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 resulting male chimeric animals were crossed to C57BL/6J females, and then 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)
000239 STOCK Jag2sm/J
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Jag2tm1Grid/Jag2+
involves: 129S1/Sv * C57BL/6J
- hearing/vestibular/ear phenotype
- increased cochlear hair cell number
- heterozygotes exhibit a slight but insignificant increase in average IHC density and total number relative to wild-type mice (MGI Ref ID J:53432)
- increased cochlear inner hair cell number
- heterozygotes display a relatively high incidence of IHC duplications relative to wild-type mice (MGI Ref ID J:53432)
- nervous system phenotype
- increased cochlear hair cell number
- heterozygotes exhibit a slight but insignificant increase in average IHC density and total number relative to wild-type mice (MGI Ref ID J:53432)
- increased cochlear inner hair cell number
- heterozygotes display a relatively high incidence of IHC duplications relative to wild-type mice (MGI Ref ID J:53432)
Jag2tm1Grid/Jag2tm1Grid
involves: 129S1/Sv * C57BL/6J
- mortality/aging
- complete perinatal lethality
- all homozygotes die within a few minutes after birth because of craniofacial defects (MGI Ref ID J:46930)
- respiratory system phenotype
- respiratory distress
- homeostasis/metabolism phenotype
- cyanosis
- newborn homozygotes become rapidly cyanotic (MGI Ref ID J:46930)
- craniofacial phenotype
- absent maxillary shelf (MGI Ref ID J:46930)
- absent palatine shelf (MGI Ref ID J:46930)
- cleft secondary palate
- at E18 (~1 day prior to birth), all homozygotes display a bilateral cleft of the secondary palate (MGI Ref ID J:46930)
- failure of palatal shelf elevation
- palatal shelves fail to elevate and fuse in the dorsal midline (MGI Ref ID J:46930)
- palatal shelf fusion with tongue or mandible
- at E18 (~1 day prior to birth), homozygotes display fusion of the tongue with the unelevated palatal shelves, preventing proper formation of the oral cavity (MGI Ref ID J:46930)
- embryogenesis phenotype
- thick apical ectodermal ridge
- limbs/digits/tail phenotype
- abnormal foot plate morphology
- at E13.5, mutant foot plates are rounder and do not exhibit the same degree of interdigital clefting as wild-type foot plates (MGI Ref ID J:46930)
- abnormal phalanx morphology
- syndactyly
- newborn homozygotes exhibit syndactyly of the fore- and hindlimbs (MGI Ref ID J:46930)
- syndactyly is associated with reduced interdigital cell death in digits 2, 3, and 4, and often involves soft tissue fusions (MGI Ref ID J:46930)
- hindlimbs are more severely affected than forelimbs (MGI Ref ID J:46930)
- thick apical ectodermal ridge
- digestive/alimentary phenotype
- absent maxillary shelf (MGI Ref ID J:46930)
- absent palatine shelf (MGI Ref ID J:46930)
- cleft secondary palate
- at E18 (~1 day prior to birth), all homozygotes display a bilateral cleft of the secondary palate (MGI Ref ID J:46930)
- failure of palatal shelf elevation
- palatal shelves fail to elevate and fuse in the dorsal midline (MGI Ref ID J:46930)
- palatal shelf fusion with tongue or mandible
- at E18 (~1 day prior to birth), homozygotes display fusion of the tongue with the unelevated palatal shelves, preventing proper formation of the oral cavity (MGI Ref ID J:46930)
- immune system phenotype
- abnormal gamma-delta T cell differentiation
- abnormal thymus morphology
- at E18 (~1 day prior to birth), homozygotes display altered thymic morphology (MGI Ref ID J:46930)
- abnormal thymus medulla morphology
- at E18, both the number and the size of developing medullary regions are reduced (MGI Ref ID J:46930)
- decreased gamma-delta T cell number
- the total percentage of gamma-delta T cells, as well as those among the CD4-/CD8- double negative subset, is about one-half that observed in wild-type thymi (MGI Ref ID J:46930)
- hearing/vestibular/ear phenotype
- abnormal cochlear outer hair cell morphology
- at E18, patterning in OHC rows is much more irregular than in wild-type (MGI Ref ID J:62727)
- abnormal orientation of inner hair cell stereociliary bundles
- at E18, homozygotes often exhibit abnormal orientation of IHC stereociliary bundles (MGI Ref ID J:53432)
- decreased organ of Corti supporting cell number
- at E18, the overall pattern of non-sensory supporting cells is present; however, some regions appear to contain a reduced number of supporting cell nuclei (MGI Ref ID J:53432)
- some pairs of IHCs appear to be in contact with one another, suggesting absence of interdigitating supporting cells at these positions (MGI Ref ID J:53432)
- increased cochlear hair cell number (MGI Ref ID J:62727)
- increased cochlear inner hair cell number (MGI Ref ID J:62727)
- at E18, homozygotes display multiple IHC duplications, resulting in the addition of a nearly complete second row of IHCs (MGI Ref ID J:53432)
- increased cochlear outer hair cell number (MGI Ref ID J:62727)
- at E18, homozygotes contain four rather than three rows of OHCs in some regions of the sensory epithelium (MGI Ref ID J:53432)
- nervous system phenotype
- abnormal cochlear outer hair cell morphology
- at E18, patterning in OHC rows is much more irregular than in wild-type (MGI Ref ID J:62727)
- abnormal orientation of inner hair cell stereociliary bundles
- at E18, homozygotes often exhibit abnormal orientation of IHC stereociliary bundles (MGI Ref ID J:53432)
- increased cochlear hair cell number (MGI Ref ID J:62727)
- increased cochlear inner hair cell number (MGI Ref ID J:62727)
- at E18, homozygotes display multiple IHC duplications, resulting in the addition of a nearly complete second row of IHCs (MGI Ref ID J:53432)
- increased cochlear outer hair cell number (MGI Ref ID J:62727)
- at E18, homozygotes contain four rather than three rows of OHCs in some regions of the sensory epithelium (MGI Ref ID J:53432)
- hematopoietic system phenotype
- abnormal gamma-delta T cell differentiation
- abnormal thymus morphology
- at E18 (~1 day prior to birth), homozygotes display altered thymic morphology (MGI Ref ID J:46930)
- abnormal thymus medulla morphology
- at E18, both the number and the size of developing medullary regions are reduced (MGI Ref ID J:46930)
- decreased gamma-delta T cell number
- the total percentage of gamma-delta T cells, as well as those among the CD4-/CD8- double negative subset, is about one-half that observed in wild-type thymi (MGI Ref ID J:46930)
- skeleton phenotype
- abnormal phalanx morphology
- absent maxillary shelf (MGI Ref ID J:46930)
- absent palatine shelf (MGI Ref ID J:46930)
- cellular phenotype
- abnormal gamma-delta T cell differentiation
Jag2tm1Grid/Jag2tm1Grid
involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J
- mortality/aging
- complete postnatal lethality
- mice do not survive postnatally (MGI Ref ID J:132241)
- hearing/vestibular/ear phenotype
- abnormal orientation of cochlear hair cell stereociliary bundles
- hair cell stereocilia bundles exhibit some disorganization (MGI Ref ID J:132241)
- increased cochlear inner hair cell number (MGI Ref ID J:132241)
- increased cochlear outer hair cell number (MGI Ref ID J:132241)
- nervous system phenotype
- abnormal orientation of cochlear hair cell stereociliary bundles
- hair cell stereocilia bundles exhibit some disorganization (MGI Ref ID J:132241)
- increased cochlear inner hair cell number (MGI Ref ID J:132241)
- increased cochlear outer hair cell number (MGI Ref ID J:132241)
This mouse can be used to support research in many areas including:
Jag2tm1Grid relatedDevelopmental Biology Research
Craniofacial and Palate Defects
congenital cleft palate
Skeletal Defects
syndactyly
Neurobiology Research
Hearing Defects
Research Tools
Immunology and Inflammation Research
specific T cell deficiency
Sensorineural Research
Hearing Defects
Developmental Biology Research
Craniofacial and Palate Defects
congenital cleft palate
Embryonic Lethality (Homozygous)
Postnatal Lethality
Homozygous
Skeletal Defects
syndactyly
Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
specific T cell deficiency
Internal/Organ Research
Thymus Defects
Sensorineural Research
Hearing Defects
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Jag2tm1Grid | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Tom Gridley | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Jag2-; Jag2deltaDSL; | ||
| Mutation Made By | Tom Gridley, Maine Medical Center Research Institute | ||
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| ES Cell Line Name | CJ7 | ||
| ES Cell Line Strain | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| Gene Symbol and Name | Jag2, jagged 2 | ||
| Chromosome | 12 | ||
| Gene Common Name(s) | D12Ggc2e; DNA segment, Chr 12, G. Consalez 2, expressed; HJ2; SER2; Serh; serrate homolog (Drosophila); sm; syndactylism; | ||
| Molecular Note | The gene was disrupted by replacement of a 5 kb region with a PGK-neo cassette via recombination resulting in deletion of the DSL domain and half of the first EGF repeat. The absence of the DSL domain-containing sequence was confirmed by Southern blot analysis. [MGI Ref ID J:46930] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Jag2tm1Grid, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Jiang R; Lan Y; Chapman HD; Shawber C; Norton CR; Serreze DV; Weinmaster G; Gridley T. 1998. Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice. Genes Dev 12(7):1046-57. [PubMed: 9531541] [MGI Ref ID J:46930]
Additional References
Jag2tm1Grid relatedAlappat SR; Zhang Z; Suzuki K; Zhang X; Liu H; Jiang R; Yamada G; Chen Y. 2005. The cellular and molecular etiology of the cleft secondary palate in Fgf10 mutant mice. Dev Biol 277(1):102-13. [PubMed: 15572143] [MGI Ref ID J:95764]
Blackburn J; Ohazama A; Kawasaki K; Otsuka-Tanaka Y; Liu B; Honda K; Rountree RB; Hu Y; Kawasaki M; Birchmeier W; Schmidt-Ullrich R; Kinoshita A; Schutte BC; Hammond NL; Dixon MJ; Sharpe PT. 2012. The role of Irf6 in tooth epithelial invagination. Dev Biol 365(1):61-70. [PubMed: 22366192] [MGI Ref ID J:184926]
Casey LM; Lan Y; Cho ES; Maltby KM; Gridley T; Jiang R. 2006. Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development. Dev Dyn 235(7):1830-1844. [PubMed: 16607638] [MGI Ref ID J:108824]
Jin JZ; Tan M; Warner DR; Darling DS; Higashi Y; Gridley T; Ding J. 2010. Mesenchymal cell remodeling during mouse secondary palate reorientation. Dev Dyn 239(7):2110-7. [PubMed: 20549719] [MGI Ref ID J:161213]
Kiernan AE; Cordes R; Kopan R; Gossler A; Gridley T. 2005. The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear. Development 132(19):4353-62. [PubMed: 16141228] [MGI Ref ID J:132241]
Lanford PJ; Lan Y; Jiang R; Lindsell C; Weinmaster G; Gridley T ; Kelley MW. 1999. Notch signalling pathway mediates hair cell development in mammalian cochlea [see comments] Nat Genet 21(3):289-92. [PubMed: 10080181] [MGI Ref ID J:53432]
Mitsiadis TA; Graf D; Luder H; Gridley T; Bluteau G. 2010. BMPs and FGFs target Notch signalling via jagged 2 to regulate tooth morphogenesis and cytodifferentiation. Development 137(18):3025-35. [PubMed: 20685737] [MGI Ref ID J:164590]
Mitsiadis TA; Regaudiat L; Gridley T. 2005. Role of the Notch signalling pathway in tooth morphogenesis. Arch Oral Biol 50(2):137-40. [PubMed: 15721140] [MGI Ref ID J:98508]
Richardson RJ; Dixon J; Jiang R; Dixon MJ. 2009. Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence. Hum Mol Genet 18(14):2632-42. [PubMed: 19439425] [MGI Ref ID J:150009]
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]
Worsley AG; Leibundgut-Landmann S; Slack E; Phng LK; Gerhardt H; Sousa CR; Macdonald AS. 2008. Dendritic cell expression of the Notch ligand jagged2 is not essential for Th2 response induction in vivo. Eur J Immunol 38(4):1043-9. [PubMed: 18350543] [MGI Ref ID J:133948]
Zhang N; Martin GV; Kelley MW; Gridley T. 2000. A mutation in the Lunatic fringe gene suppresses the effects of a Jagged2 mutation on inner hair cell development in the cochlea. Curr Biol 10(11):659-62. [PubMed: 10837254] [MGI Ref ID J:62727]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes have a perinatal lethal phenotype.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|
|
|
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
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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