C57BL/6J-Trpm4^em1Sthg/J

Stock number: 037966
Product name: TRPM4^I1029M
Research areas: Dermatology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

TRPM4^I1029M knock-in mice express a gain-of-function (GOF) isoleucine to methionine substitution at position 1029 of the transient receptor potential cation channel, subfamily M, member 4 (Trpm4) gene. Heterozygous mice treated with imiquimod develop a psoriasis-like dermatitis. These mice may be useful as a model for progressive systemic erythrokeratodermia (PDEK).

Detailed description

Trpm4 (transient receptor potential cation channel, subfamily M, member 4) encodes a calcium-activated nonselective cation channel expressed in many cell types. TRPM4^I1029M knock-in mice express a gain-of-function (GOF) isoleucine to methionine substitution at position 1029 (orthologous to human I1033M). In humans,the I1033M mutation in the heterozygous form is associated with progressive systemic erythrokeratodermia (PDEK). Mice heterozygous and homozygous for the I1029M mutation are viable and fertile and exhibit no obvious phenotype. However, heterozygous mice treated with imiquimod (IMQ) develop inflammation characterized by ear thickening, erythema and scale, increased proliferation of keratinocytes, increased epidermal thickness, enhanced inflammation characterized by an accumulation of CCR6-expressing γδ-low T cells, and increased expression of IL17A.

Development

CRISPR/cas9 endonuclease-mediated genome editing was used to create an isoleucine to methionine substitution at position 1029 (p.I1029M, c.C3087G) in exon 20 of the Trpm4 locus on chromosome 7. The mutation is a variant identified in PSEK patients. Single guide RNA (CAGGTTGAGCA ACAGGATATTGG) cas9 endonuclease and single stranded donor oligos were introduced into C57BL/6J-derived fertilized eggs by pronuclear injection. Embryos were transferred to pseudopregnant females, and correctly targeted pups were bred to C57BL/6J mice for germline transmission. The colony was maintained on C57BL/6J. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Trpm4^em1Sthg
Name: endonuclease-mediated mutation 1, Samuel T Hwang
MGI accession ID: MGI:7388564
Generation method: Endonuclease-mediated
Attributes: Not Specified
Synonyms: TRPM4^I1029M
Marker symbol: Trpm4
Marker name: transient receptor potential cation channel, subfamily M, member 4
Marker synonyms: 1110030C19Rik; EKVP6; hTRPM4; LTrpC4; LTrpC-4; Mls2s; PFHB1B; TRPM4B
Chromosome: 7
Strain of origin: C57BL/6J
Molecular note: CRISPR-targeting introduced the mutation resulting in the amino acid substitution of isoleucine with methionine at position 1029 (I1029M).