{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:45:06Z","timestamp":1788975906805,"version":"build-2803163510"},"reference-count":66,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009340","name":"Children\u2019s Discovery Institute","doi-asserted-by":"crossref","award":["FR-2021-933"],"award-info":[{"award-number":["FR-2021-933"]}],"id":[{"id":"10.13039\/100009340","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["DBI-1827534"],"award-info":[{"award-number":["DBI-1827534"]}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["NS110793,HL146601,HL128370"],"award-info":[{"award-number":["NS110793,HL146601,HL128370"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,8]]},"abstract":"<jats:p>\n                    DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift-null deletion in\n                    <jats:italic>Dnaaf5<\/jats:italic>\n                    . Litters with\n                    <jats:italic>Dnaaf5<\/jats:italic>\n                    heteroallelic variants showed distinct missense and null gene dosage effects. Homozygosity for the null\n                    <jats:italic>Dnaaf5<\/jats:italic>\n                    alleles was embryonic lethal. Compound heterozygous animals with the missense and null alleles showed severe disease manifesting as hydrocephalus and early lethality. However, animals homozygous for the missense mutation had improved survival, with partially preserved cilia function and motor assembly observed by ultrastructure analysis. Notably, the same variant alleles exhibited divergent cilia function across different multiciliated tissues. Proteomic analysis of isolated airway cilia from mutant mice revealed reduction in some axonemal regulatory and structural proteins not previously reported in\n                    <jats:italic>DNAAF5<\/jats:italic>\n                    variants. Transcriptional analysis of mouse and human mutant cells showed increased expression of genes coding for axonemal proteins. These findings suggest allele-specific and tissue-specific molecular requirements for cilia motor assembly that may affect disease phenotypes and clinical trajectory in motile ciliopathies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.168836","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T17:07:24Z","timestamp":1682615244000},"source":"Crossref","is-referenced-by-count":24,"title":["The effect of Dnaaf5 gene dosage on primary ciliary dyskinesia phenotypes"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5352-1948","authenticated-orcid":true,"given":"Amjad","family":"Horani","sequence":"first","affiliation":[{"name":"Department of Pediatrics,"},{"name":"Department of Cell Biology and Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepesh Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of 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