B6;129X1-Gadd45b^tm1Daa/J

Stock number: 029141
Product name: Gadd45b knock-out
Research areas: Apoptosis Research, Neurobiology Research, Research Tools

Description

This Gadd45b knock-out strain is useful in studies of memory and synaptic plasticity, and apoptosis.

Detailed description

The targeted Gadd45b gene encodes a sensor of physiological and environmental stress that mediates activation of the p38/JNK pathway. These mice carry a knock-out allele of the Gadd45b gene in which the entire protein coding region and flanking sequence has been replaced by a NEO cassette. No gene product (mRNA) is detected by Northern blot analysis of bone marrow cells from homozygotes. Mice that are homozygous for the targeted mutation are viable and fertile. Bone marrow cells isolated from homozygotes are more sensitive to UV radiation, daunorubicin, or VP-16, exhibiting increased apoptosis. Homozygotes have slightly increased liver mass, but smaller hepatocytes, with a delayed drug-induced hyperplasia response compared to wildtype controls. Knock-out mice exhibit enhanced persisting memory tasks of motor performance, aversive conditioning and spatial navigation.

Development

A targeting vector containing a NEO cassette (in antisense transcriptional orientation) was used to disrupt 301 bp of the proximal promoter, the 5' untranslated region of the mRNA, the entire protein coding region and 425 bp of the 3' untranslated region of the targeted Gadd45b gene. The construct was electroporated into 129X1/SvJ derived ESVJ-1183 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to C57BL/6 female mice. Heterozygotes were intercrossed to generate homozygotes. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Gadd45b^tm1Daa
Name: targeted mutation 1, Dan A Liebermann
MGI accession ID: MGI:3608798
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Gadd45b
Marker name: growth arrest and DNA-damage-inducible 45 beta
Chromosome: 10
Strain of origin: 129X1/SvJ
Molecular note: 301 bp of the proximal promoter, the 5' untranslated region of the mRNA, the entire protein coding region and 425 bp of the 3' untranslated region were replaced by a 1.9 kb neo cassette (transcription of neo is antisense) from the plasmid pGT-N29 via homologous recombination.