{"doi":"10.1093/hmg/ddae161","title":"Loss of paired immunoglobin-like type 2 receptor B gene associated with age-related macular degeneration impairs photoreceptor function in mouse retina","abstract":"Genome-wide association studies have uncovered mostly non-coding variants at over 60 genetic loci linked to susceptibility for age-related macular degeneration (AMD). To ascertain the causal gene at the PILRB/PILRA locus, we used a CRISPR strategy to produce germline deletions in the mouse paired immunoglobin-like type 2 receptor (Pilr) genes that encode highly related activating (PILRB) and inhibitory (PILRA) receptors. We show that a combined loss of Pilrb1 and Pilrb2, but not Pilra, leads to an early but relatively stationary defect as the electroretinography (ERG) amplitudes of Pilrb1/2-/- mice exhibit a marked reduction as early as postnatal day 15 and do not show additional significant decrease at 3 and 12-months. No alterations are evident in Müller glia, microglia, bipolar, amacrine and horizontal cells based on immunohistochemistry using cell-type specific markers. PILRB immunostaining is specifically detected at the proximal part of photoreceptor outer segment. Reduced expression of select calcium-regulated phototransduction and synapse-associated proteins, including GCAP1 and 2, PDE6b, AIPL1, PSD95, and CTBP1 indicates dysregulation of calcium homeostasis as a possible mechanism of retinal phenotype in Pilrb1/2-/- mice. Our studies suggest a novel function of PILRB in retinal photoreceptors and an association of PILRB, but not PILRA, with AMD pathogenesis.","journal":"Human Molecular Genetics","year":2024,"id":461608,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9347,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":565088,"name":"Nivedita Singh","orcid":"0000-0001-5919-1161","position":1,"is_corresponding":false},{"id":1111894,"name":"Lina Zelinger","orcid":"0000-0003-3028-7172","position":2,"is_corresponding":false},{"id":301400,"name":"Zachary Batz","orcid":"0000-0002-4483-2402","position":3,"is_corresponding":false},{"id":325255,"name":"Jacob Nellissery","orcid":"0000-0002-1209-664X","position":4,"is_corresponding":false},{"id":540893,"name":"Noor D. White","orcid":"0000-0002-9510-3744","position":5,"is_corresponding":false},{"id":402015,"name":"Haohua Qian","orcid":"0000-0002-1114-4697","position":6,"is_corresponding":false},{"id":274270,"name":"Tiansen Li","orcid":"0000-0002-9537-2573","position":7,"is_corresponding":false},{"id":340527,"name":"Robert N. Fariss","orcid":"0000-0003-3227-7170","position":8,"is_corresponding":false},{"id":286497,"name":"Lijin Dong","orcid":"0000-0001-7401-9511","position":9,"is_corresponding":false},{"id":54657,"name":"Anand Swaroop","orcid":"0000-0002-1975-1141","position":10,"is_corresponding":false},{"id":821586,"name":"Partha Narayan Dey","orcid":"0000-0001-9992-7313","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:04:16.410510Z","pmid":"39532089","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}