B6.129-Trpv3^tm1Apat/J

Stock number: 010773
Research areas: Cell Biology Research, Neurobiology Research, Sensorineural Research

Description

This TRPV3 mutant allele harbors a deletion of Trpv3 exons 13 and 14, resulting in low levels of truncated TRPV3 transcript and strong deficits in responses to innocuous and noxious heat stimuli.

Detailed description

Homozygous (TRPV3^-/-) mice are viable and fertile, with deletion of Trpv3 (transient receptor potential cation channel, subfamily V, member 3) exons resulting in low levels of truncated TRPV3 transcript that does not encode the putative pore region or adjacent transmembrane domains five and six (essential domains of the ion channel). Homozygous mice lack functional TRPV3 with no abnormal affects on TRPV1/TRPV4 expression or overall dorsal root ganglia or skin anatomy. TRPV3^-/- mice have strong deficits in responses to innocuous and noxious heat stimuli, but not in other sensory modalities, and retain a residual sensitivity to warm temperatures. Compared to wildtype mice, TRPV3-deficient mice are resistant to the anxiolytic-like and antidepressive-like behavioral effects (and concomitant changes in c-Fos activation in the brain) following treatment of the TRPV3 agonist, incensole acetate. Unlike wildtype keratinocytes, TRPV3-deficient keratinocytes are not activated by camphor (warmth sensation) or incensole acetate treatment. These TRPV3 mutant mice may be useful in studying the transient receptor potential family of ion channels in environmental temperature sensations in the skin (thermoTRPs), as well as TRPV3 channels in neurological emotional regulation.

Development

A targeting vector was designed to replace a portion of exon 14 and 15 of the Trpv3 (transient receptor potential cation channel, subfamily V, member 3) gene with a PGK-Neo cassette. 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 recipient blastocysts and chimeric males were bred with C57BL/6J females to establish the colony. The donating investigator reports that TRPV3-deficient mice were subsequently backcrossed to C57BL/6J for ten generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Trpv3^tm1Apat
Name: targeted mutation 1, Ardem Patapoutian
MGI accession ID: MGI:3574024
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Trpv3
Marker name: transient receptor potential cation channel, subfamily V, member 3
Chromosome: 11
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: The exons encoding the putative pore region and adjacent transmembrane segments five and six were deleted by homologous recombination. RT-PCR of skin demonstrated that mutants lacked the wild-type protein. Presence of low levels of a truncated transcript was shown.
General note: Per a personal communication from the laboratory of Dr. Ardem Patapoutian, the gene was targeted in the R1 embryonic stem cell line, not in the CJ7 line as stated in the original reference for this mutation.