Trpc6 (transient receptor potential cation channel, c6) knockout mice exhibit increased vascular smooth muscle contractility and elevated systemic blood pressure.
Lutz Birnbaumer, National Institutes of Health
Trpc6 (transient receptor potential cation channel, c6) encodes a receptor activated calcium channel and is highly expressed in pulmonary and vascular smooth muscle cells. Homozygous knockout mice exhibit increased agonist-induced contractility in isolated aortic rings and elevated systemic blood pressure. Smooth muscle cells have higher basal cation entry, increased TRPC-carried cation currents and more depolarized membrane potentials as compared to controls. Intrinsically photosensitive retinal ganglion cells (ipRGCs) from null mice exhibit some altered responses to light stimulation.
This strain may be useful for studying the control of vascular smooth muscle tone and TRPC involvement in the melanopsin signaling pathway.
A targeting vector containing a neomycin resistance cassette was used to disrupt exon 7. In the protein this results in the loss of transmembrane segments 4 and 5 and part of the pore region. The construct was electroporated into 129S/SvEv-derived EK.CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice for one generation. A homozygous colony was established and maintained by interbreeding. Upon arrival, mice were bred to C57BL/6J for 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Lutz Birnbaumer|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Trpc6, transient receptor potential cation channel, subfamily C, member 6|
|Strain of Origin||129S/SvEv-Gpi1c|
|General Note||The reported phenotypes did not differ among mice from backcross generations N1 through N10 to C57BL/6J. |
Trpc3 mRNA is elevated 3- to 5-fold in thoracic aorta and 2-fold in cerebral arteries of mutant mice compared to wild-type littermates, and Trpc7 mRNA is increased 2-fold in mutant cerebral arteries; levels of other Trpc mRNAs do not differ between mutant and control vessels.
|Molecular Note||A neomycin resistance cassette replaces exon 7, which encodes amino acids 584-670 comprising transmembrane domains 4 and 5 and a small part of the pore domain. Segments of mRNA upstream or downstream of the deletion cannot be amplified by RT-PCR from total lung RNA of homozygous mutant mice.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the Trpc6- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37345 in your Materials and Methods section.