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.
Dr. Thomas C. Sudhof, Stanford University School of Medicine
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Nrxn2 | neurexin II |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Nrxn3 | neurexin III |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Nrxn1 | neurexin I |
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.
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 Name | targeted mutation 1, Thomas C Sudhof |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Nrxn2, neurexin II |
Gene Synonym(s) | |
Strain of Origin | 129 |
Chromosome | 19 |
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.. |
Mutations Made By | Dr. Thomas Sudhof, Stanford University School of Medicine |
Allele Name | targeted mutation 1, Thomas C Sudhof |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Nrxn3, neurexin III |
Gene Synonym(s) | |
Strain of Origin | 129 |
Chromosome | 12 |
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. |
Mutations Made By | Dr. Thomas Sudhof, Stanford University School of Medicine |
Allele Name | targeted mutation 1, Thomas C Sudhof |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Nrxn1alphaKO; SKO2 |
Gene Symbol and Name | Nrxn1, neurexin I |
Gene Synonym(s) | |
Strain of Origin | 129 |
Chromosome | 17 |
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. |
When maintained as a live colony, animals homozygous for Nrxn2 and heterozygous for Nrxn1 and Nrxn3 are intercrossed.
When using the B6;129-Nrxn3tm1Sud Nrxn1tm1Sud Nrxn2tm1Sud/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006377 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Nrxn3<tm1Sud>, Heterozygous or wildtype for Nrxn1<tm1Sud>, heterozygous for Nrxn2<tm1Sud> |
Frozen Mouse Embryo | B6;129-Nrxn3<tm1Sud> Nrxn1<tm1Sud> Nrxn2<tm1Sud>/J Frozen Em | $2595.00 |
Frozen Mouse Embryo | B6;129-Nrxn3<tm1Sud> Nrxn1<tm1Sud> Nrxn2<tm1Sud>/J Frozen Em | $2595.00 |
Frozen Mouse Embryo | B6;129-Nrxn3<tm1Sud> Nrxn1<tm1Sud> Nrxn2<tm1Sud>/J Frozen Em | $3373.50 |
Frozen Mouse Embryo | B6;129-Nrxn3<tm1Sud> Nrxn1<tm1Sud> Nrxn2<tm1Sud>/J Frozen Em | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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