biostudies-literatureZhou YDepartment of Ophthalmology and Visual Sciences as well as a Career Development AwardNCATS NIH HHSNEI NIH HHSNIH/NEINCI NIH HHSNINDS NIH HHSNIHNIH HHS257https://www.ebi.ac.uk/biostudies/studies/S-EPMC10854584biostudies-literatureUnknown13(3)TRPM3 belongs to the melastatin sub-family of transient receptor potential (TRPM) cation channels and has been shown to function as a steroid-activated, heat-sensitive calcium ion (Ca²⁺) channel. A missense substitution (p.I65M) in the TRPM3 gene of humans (<i>TRPM3</i>) and mice (<i>Trpm3</i>) has been shown to underlie an inherited form of early-onset, progressive cataract. Here, we model the pathogenetic effects of this cataract-causing mutation using 'knock-in' mutant mice and human cell lines. <i>Trpm3</i> and its intron-hosted micro-RNA gene (<i>Mir204</i>) were strongly co-expressed in the lens epithelium and other non-pigmented and pigmented ocular epithelia. Homozygous <i>Trpm3</i>-mutant lenses displayed elevated cytosolic Ca²⁺ levels and an imbalance of sodCellsA Cataract-Causing Mutation in the TRPM3 Cation Channel Disrupts Calcium Dynamics in the Lens.PMC10854584UL1 TR002345NS103350UL1TR002345R01 EY028899EY028899EY009532P30 EY002687R01 EY029171P30 CA091842R01 NS103350R01 EY009532EY02687EY028899, EY02687, NS103350, EY009532EY029171P30 CA91842Ruzycki PAShiels AGuo ZBennett TMCao YQZhou YShahidullah MDelamere NAfalseA Cataract-Causing Mutation in the TRPM3 Cation Channel Disrupts Calcium Dynamics in the Lens.TRPM3 belongs to the melastatin sub-family of transient receptor potential (TRPM) cation channels and has been shown to function as a steroid-activated, heat-sensitive calcium ion (Ca²⁺) channel. A missense substitution (p.I65M) in the TRPM3 gene of humans (<i>TRPM3</i>) and mice (<i>Trpm3</i>) has been shown to underlie an inherited form of early-onset, progressive cataract. Here, we model the pathogenetic effects of this cataract-causing mutation using 'knock-in' mutant mice and human cell lines. <i>Trpm3</i> and its intron-hosted micro-RNA gene (<i>Mir204</i>) were strongly co-expressed in the lens epithelium and other non-pigmented and pigmented ocular epithelia. Homozygous <i>Trpm3</i>-mutant lenses displayed elevated cytosolic Ca²⁺ levels and an imbalance of sod2024-01-01T00:00:00Z2024 Jan2026-07-03T03:15:29.642Z2025-04-04T13:34:13.059ZS-EPMC108545843833464910.3390/cells13030257