B6.129-Bc1^tm1Jbro/J

Stock number: 018417
Research areas: Neurobiology Research

Description

In this strain a NEO cassette replaces the coding region of the Bc1 (brain cytoplasmic RNA 1) gene. These mice exhibit neuronal hyperexcitability and have applications in studies related to synaptic dysregulation.

Detailed description

Brain cytoplasmic RNAs regulate translation initiation. The neuronal brain cytoplasmic RNA 1, gene (Bc1), is involved in synaptic plasticity. These mice carry a knockout allele for the Bc1 gene, in which the entire coding region has been replaced by a NEO cassette. On the mixed B6;129 background, homozygotes are more susceptible to audiogenic seizures due to neuronal hyperexcitability. Most homozygotes (84% on the B6;129 background) exposed to auditory stimulation (120dB alarm) exhibit generalized clonic-tonic convulsive seizures after 2 minutes of exposure, but recover after approximately 1 minute. Approximately a quarter of the mice die during the seizures. Homozygotes display reduced exploration behavior and increased anxiety. The Donating Investigator reports that on the C57BL/6 congenic background, homozygotes aged 18 - 21 days, exhibit excessive grooming behavior, and are not susceptible to audiogenic seizures.

Mice that are homozygous for the targeted mutation are viable and fertile. No transcript is detected by Northern blot analysis of brain, testes, and liver. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.

When crossed to mice homozygous for the Fmr1^tm1Cgr targeted mutation (Stock No. 003024), the double mutant mice exhibit CA3 pyramidal cell hyperexcitability that is more severe than observed in the single mutant lines.

Development

A targeting vector containing a PGK-NEO cassette was used to disrupt the entire coding region of the gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺ derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. Heterozygotes were intercrossed to generate homozygotes. The mice were then backcrossed to C57BL/6 for 15 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Bc1^tm1Jbro
Name: targeted mutation 1, Jurgen Brosius
MGI accession ID: MGI:2677614
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Bc1
Marker name: brain cytoplasmic RNA 1
Chromosome: 7
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: The endogenous gene was replaced with a neomycin selection cassette inserted by homologous recombination. Northern blot analysis confirmed the absence of transcript in homozygous mutant mice.