Mice that are homozygous null for Tac1 have significantly reduced nociceptive pain responses to moderate to intense stimuli, and neurogenic inflammation is absent. Mutant mice are resistant to kainate-induced seizures and neurotoxicity. These mice provide a useful tool for studying the contribution of tachykinin peptides to pain processing and inflammatory disease states.
Allan Basbaum, Univ. California, San Francisco
Mice that are homozygous null for the Tac1 gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Tac1 protein products (substance P or neurokinin A) are not immunodetectable. These mice have significantly reduced nociceptive pain responses to moderate to intense stimuli. Neurogenic inflammation is absent. Mutant mice are resistant to kainate-induced seizures and neurotoxicity. These mice provide a useful tool for studying the contribution of tachykinin peptides to pain processing and inflammatory disease states.
A targeting vector containing neomycin resistance and thymidine kinase genes was used to disrupt the Tac1 gene, replacing the substance P coding exon (3) with neo and deleting the neurokinin A coding exon (6). The construct was introduced into CB1-4 embryonic stem cells. Correctly targeted ES cells were injected into CD-1 morula-stage zygotes. The donating investigator reports that the resulting chimeric animals were backcrossed to C57BL/6J mice.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Allan Basbaum|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||PPT-A-; PPTA-; SPP-|
|Gene Symbol and Name||Tac1, tachykinin 1|
|Strain of Origin||C57BL/6J x (Rb(11.16)2H x Rb(16.17)32Lub)F1|
|Molecular Note||Insertion of a PGK-neomycin resistance cassette into the gene replaced a coding region in exon 3 and deleted a coding region in exon 6. Immunoreactivity was not detected in the lumbar spinal cord of homozygous mutant mice.|
|Mutations Made By|| |
Yuqing Cao, Stanford University Medical Center
When using the PPT-A KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004103 in your Materials and Methods section.