B6;129-Nrxn3^tm1Sud Nrxn1^tm1Sud Nrxn2^tm1Sud/J

Stock number: 006377
Research areas: Neurobiology Research

Description

Mice that are homozygous for neurexin I, II and III gene mutations die within 24 hours of birth. Although newborn mice are initially capable of directed movements and react to tactile stimuli, the integrative brain functions required for breathing are impaired.

Detailed description

Mice that are homozygous for all three targeted mutations die within 24 hours of birth. Although newborn mice are initially capable of directed movements and react to tactile stimuli, the integrative brain functions required for breathing are impaired. At birth, the body and brain weights of triple targeted mutation mice are indistinguishable. Assymetric type I and symmetric type II synapses in triple homozygotes are ultrastructurally normal. The density of symmetric (presumptive inhibitory) synapses are reduced whereas the density of asymmetric (presumptive excitatory) synapses are not. Neurotransmitter release is generally impaired due to reduced Ca²⁺ channel function. No protein product from any of the targeted genes is detected in brain tissue. Quantification of the levels of 22 other neuronal proteins detected no major changes. This mutant mouse strain represents a model that may be useful in studies of synaptic vesicle exocytosis mechanisms in neurons.

Development

A targeting vector containing a neomycin resistance gene was used to replace the first coding exons of the three targeted genes. The construct was electroporated into 129/Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric animals were crossed with C57BL/6 mice.

Allele

Symbol: Nrxn3^tm1Sud
Name: targeted mutation 1, Thomas C Sudhof
MGI accession ID: MGI:3042720
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Nrxn3
Marker name: neurexin III
Chromosome: 12
Strain of origin: 129
Molecular note: A neo cassette replaced the first exon, which contains the complete 5' UTR, start codon, signal peptide and the first LNS domain. Immunoblotting of mutant brain confirmed lack of protein expression.

Allele

Symbol: Nrxn1^tm1Sud
Name: targeted mutation 1, Thomas C Sudhof
MGI accession ID: MGI:3042794
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Nrxn1
Marker name: neurexin I
Chromosome: 17
Strain of origin: 129
Molecular note: A neo cassette replaced the first exon, which contains the complete 5' UTR, start codon, signal peptide and the first LNS domain. Protein was undetected by Western blot analysis of mutant mice.

Allele

Symbol: Nrxn2^tm1Sud
Name: targeted mutation 1, Thomas C Sudhof
MGI accession ID: MGI:3042719
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Nrxn2
Marker name: neurexin II
Chromosome: 19
Strain of origin: 129
Molecular note: A neo cassette replaced the first exon, which contains the complete 5' UTR, start codon, signal peptide and the first LNS domain. Immunoblotting of mutant brain confirmed lack of protein expression. This knock-out affects the alpha isoform specifically. The beta isoform, transcribed from a downstream promoter, is not affected..