129S-Ywhae^tm1Awb/J

Stock number: 008715
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

Mice carrying this targeted mutation of Ywhae (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide) exhibit hippocampal defects, neuronal migration abnormalities, and increased apoptosis in the brain. This mutant mouse strain may be useful in studies of Miller-Dieker Lissencephaly Syndrome and neuronal migration during brain development.

Detailed 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. Most homozygotes die at birth, less than 1% of homozygotes survive to adulthood. Survivors remain smaller in size than wildtype controls. No gene product (protein) is detected by immunoblot analysis of brain tissue from homozygotes. Homozygotes exhibit hippocampal defects with thinning of the cortex, hippocampal pyramidal cell layer disorganization and neuronal migration abnormalities. Heterozygotes exhibit less severe hippocampal defects. Mutants have increased apoptosis in the brain. This mutant mouse strain may be useful in studies of Miller-Dieker Lissencephaly Syndrome and neuronal migration during brain development.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt parts of exons 2 and 3. The construct was electroporated into 129S6/SvEvTac derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to 129S6 mice. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least one generation to establish the colony.

Allele

Symbol: Ywhae^tm1Awb
Name: targeted mutation 1, Anthony Wynshaw-Boris
MGI accession ID: MGI:2667341
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ywhae
Marker name: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide
Chromosome: 11
Strain of origin: 129S6/SvEvTac
Molecular note: Exons 2 and 3 were partially replaced by a neomycin resistance gene and a loxP site. Immunoblot analysis indicated the complete absence of gene product in homozygotes and a reduction by half in heterozygotes.