B6.129S1-Jag2^tm1Grid/J

Stock number: 010546
Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

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.

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.

Allele

Symbol: Jag2^tm1Grid
Name: targeted mutation 1, Tom Gridley
MGI accession ID: MGI:2657215
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Jag2
Marker name: jagged 2
Chromosome: 12
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
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.