Overview

Homozygous Jag2^deltaDSL 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.

Donating Investigator

Thomas Gridley, Maine Medical Center Research Institute

Genetic overview

Genetic Background	Generation

Jag2^tm1Grid

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Jag2	jagged 2

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Research Applications

Internal/Organ Research
Developmental Biology Research
Sensorineural Research
Neurobiology Research
Immunology, Inflammation and Autoimmunity Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):1046-57PubMed: 9531541 MGI: J:46930

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Genetics

Jag2^tm1Grid

Allele Symbol: Jag2^tm1Grid

Allele Name	targeted mutation 1, Tom Gridley
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Jag2^-; Jag2^deltaDSL
Gene Symbol and Name	Jag2, jagged 2
Gene Synonym(s)
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	12
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.
Mutations Made By	Thomas Gridley, Maine Medical Center Research Institute

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Jag2^tm1Grid related

Internal/Organ Research
- Thymus Defects
Developmental Biology Research
- Craniofacial and Palate Defects
  - congenital cleft palate
- Embryonic Lethality (Homozygous)
- Skeletal Defects
  - syndactyly
- Postnatal Lethality
  - Homozygous
Sensorineural Research
- Hearing Defects
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - specific T cell deficiency

Developmental Biology Research
- Skeletal Defects
  - syndactyly
- Craniofacial and Palate Defects
  - congenital cleft palate
Neurobiology Research
- Hearing Defects
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - specific T cell deficiency
Sensorineural Research
- Hearing Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Jag2^tm1Grid/Jag2⁺
involves: 129S1/Sv * C57BL/6J

hearing/vestibular/ear phenotype

increased cochlear inner hair cell number
- heterozygotes display a relatively high incidence of IHC duplications relative to wild-type mice

increased cochlear hair cell number
- heterozygotes exhibit a slight but insignificant increase in average IHC density and total number relative to wild-type mice

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

increased cochlear inner hair cell number
- heterozygotes display a relatively high incidence of IHC duplications relative to wild-type mice

Genotype: Jag2^tm1Grid/Jag2^tm1Grid
involves: 129S1/Sv * C57BL/6J

embryo phenotype

thick apical ectodermal ridge
- however, no decreased AER programmed cell death is noted at E10.5
- at E10.5-E11.5, homozygotes display a hyperplastic AER

endocrine/exocrine gland phenotype

abnormal thymus morphology
- at E18 (~1 day prior to birth), homozygotes display altered thymic morphology

abnormal thymus medulla morphology
- at E18, both the number and the size of developing medullary regions are reduced

growth/size/body region phenotype

absent maxillary shelf

failure of palatal shelf elevation
- palatal shelves fail to elevate and fuse in the dorsal midline

absent palatine bone horizontal plate

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

cleft secondary palate
- at E18 (~1 day prior to birth), all homozygotes display a bilateral cleft of the secondary palate

hearing/vestibular/ear phenotype

increased cochlear inner hair cell number
- at E18, homozygotes display multiple IHC duplications, resulting in the addition of a nearly complete second row of IHCs

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
- some pairs of IHCs appear to be in contact with one another, suggesting absence of interdigitating supporting cells at these positions

abnormal orientation of inner hair cell stereociliary bundles
- at E18, homozygotes often exhibit abnormal orientation of IHC stereociliary bundles

increased cochlear hair cell number
- a significant reduction in the ratio of OHCs to IHCs is observed
- at E18, homozygotes exhibit a significant increase in the total number and density of cochlear hair cells, primariliy due to an increase in IHCs

increased cochlear outer hair cell number
- at E18, homozygotes contain four rather than three rows of OHCs in some regions of the sensory epithelium

abnormal cochlear outer hair cell morphology
- at E18, patterning in OHC rows is much more irregular than in wild-type

craniofacial phenotype

cleft secondary palate
- at E18 (~1 day prior to birth), all homozygotes display a bilateral cleft of the secondary palate

failure of palatal shelf elevation
- palatal shelves fail to elevate and fuse in the dorsal midline

absent maxillary shelf

absent palatine bone horizontal plate

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

hematopoietic system phenotype

abnormal gamma-delta T cell differentiation
- in contrast, differentiation of alpha-beta T cells is unaffected
- at E18, homozygotes display impaired differentiation of gamma-delta T lymphocyte lineage

abnormal thymus medulla morphology
- at E18, both the number and the size of developing medullary regions are reduced

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

abnormal thymus morphology
- at E18 (~1 day prior to birth), homozygotes display altered thymic morphology

homeostasis/metabolism phenotype

cyanosis
- newborn homozygotes become rapidly cyanotic

immune system phenotype

abnormal gamma-delta T cell differentiation
- in contrast, differentiation of alpha-beta T cells is unaffected
- at E18, homozygotes display impaired differentiation of gamma-delta T lymphocyte lineage

abnormal thymus medulla morphology
- at E18, both the number and the size of developing medullary regions are reduced

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

abnormal thymus morphology
- at E18 (~1 day prior to birth), homozygotes display altered thymic morphology

limbs/digits/tail phenotype

abnormal phalanx morphology
- several newborns exhibit splitting of the terminal phalanx of digit 2 of the hindfeet
- 5 of 13 newborn homozygotes show primary chondrogenic or secondary osseous fusions of the distal phalanges, with the hindfeet more severely affected

syndactyly
- syndactyly is associated with reduced interdigital cell death in digits 2, 3, and 4, and often involves soft tissue fusions
- hindlimbs are more severely affected than forelimbs
- newborn homozygotes exhibit syndactyly of the fore- and hindlimbs

abnormal embryonic autopod 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

thick apical ectodermal ridge
- at E10.5-E11.5, homozygotes display a hyperplastic AER
- however, no decreased AER programmed cell death is noted at E10.5

mortality/aging

perinatal lethality, complete penetrance
- all homozygotes die within a few minutes after birth because of craniofacial defects

nervous system phenotype

abnormal orientation of inner hair cell stereociliary bundles
- at E18, homozygotes often exhibit abnormal orientation of IHC stereociliary bundles

increased cochlear hair cell number
- at E18, homozygotes exhibit a significant increase in the total number and density of cochlear hair cells, primariliy due to an increase in IHCs
- a significant reduction in the ratio of OHCs to IHCs is observed

increased cochlear inner hair cell number
- at E18, homozygotes display multiple IHC duplications, resulting in the addition of a nearly complete second row of IHCs

abnormal cochlear outer hair cell morphology
- at E18, patterning in OHC rows is much more irregular than in wild-type

increased cochlear outer hair cell number
- at E18, homozygotes contain four rather than three rows of OHCs in some regions of the sensory epithelium

respiratory system phenotype

respiratory distress
- only a few are able to breathe, but all of these die within a few hours after birth with large amounts of air in the stomach and intestines
- most newborn homozygotes are unable to breathe

skeleton phenotype

abnormal phalanx morphology
- 5 of 13 newborn homozygotes show primary chondrogenic or secondary osseous fusions of the distal phalanges, with the hindfeet more severely affected
- several newborns exhibit splitting of the terminal phalanx of digit 2 of the hindfeet

absent maxillary shelf

absent palatine bone horizontal plate

digestive/alimentary phenotype

cleft secondary palate
- at E18 (~1 day prior to birth), all homozygotes display a bilateral cleft of the secondary palate

absent maxillary shelf

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

absent palatine bone horizontal plate

failure of palatal shelf elevation
- palatal shelves fail to elevate and fuse in the dorsal midline

Genotype: Jag2^tm1Grid/Jag2^tm1Grid
involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J

hearing/vestibular/ear phenotype

abnormal orientation of cochlear hair cell stereociliary bundles
- hair cell stereocilia bundles exhibit some disorganization

increased cochlear inner hair cell number

increased cochlear outer hair cell number

mortality/aging

postnatal lethality, complete penetrance
- mice do not survive postnatally

nervous system phenotype

increased cochlear inner hair cell number

increased cochlear outer hair cell number

abnormal orientation of cochlear hair cell stereociliary bundles
- hair cell stereocilia bundles exhibit some disorganization

References

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):1046-57PubMed: 9531541 MGI: J:46930

Additional - Jag2^tm1Grid related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Jag2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes have a perinatal lethal phenotype.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S1-Jag2^tm1Grid/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010546 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-type for Jag2<tm1Grid>

Related Products and Services

Frozen Mouse Embryo	B6.129S1-Jag2<tm1Grid>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S1-Jag2<tm1Grid>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S1-Jag2<tm1Grid>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S1-Jag2<tm1Grid>/J Frozen Embryo	$3373.50

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Jag2tm1Grid

Allele Symbol: Jag2tm1Grid

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Jag2tm1Grid related

Mammalian Phenotype Terms by Genotype

Genotype: Jag2tm1Grid/Jag2+involves: 129S1/Sv * C57BL/6J

hearing/vestibular/ear phenotype

nervous system phenotype

Genotype: Jag2tm1Grid/Jag2tm1Gridinvolves: 129S1/Sv * C57BL/6J

embryo phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

craniofacial phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

limbs/digits/tail phenotype

mortality/aging

nervous system phenotype

respiratory system phenotype

skeleton phenotype

digestive/alimentary phenotype

Genotype: Jag2tm1Grid/Jag2tm1Gridinvolves: 129S1/Sv * 129S1/SvImJ * C57BL/6J

hearing/vestibular/ear phenotype

mortality/aging

nervous system phenotype

References

Additional - Jag2tm1Grid related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Jag2^tm1Grid

Allele Symbol: Jag2^tm1Grid

Genotype: Jag2^tm1Grid related

Genotype: Jag2^tm1Grid/Jag2⁺
involves: 129S1/Sv * C57BL/6J

Genotype: Jag2^tm1Grid/Jag2^tm1Grid
involves: 129S1/Sv * C57BL/6J

Genotype: Jag2^tm1Grid/Jag2^tm1Grid
involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J

Additional - Jag2^tm1Grid related