Development and Initial Characterization of Pigs withDNAI1Mutations and Primary Ciliary Dyskinesia Article Swipe
Mahmoud H. Abou Alaiwa
,
B. Hilkin
,
Margaret P. Price
,
Nicholas D. Gansemer
,
Michael R. Rector
,
Mal R. Stroik
,
Linda S. Powers
,
Kristin M. Whitworth
,
Melissa Samuel
,
Akansha Jain
,
Lynda S. Ostedgaard
,
Sarah E. Ernst
,
Winter Philibert
,
Linda D. Boyken
,
Thomas O. Moninger
,
Phillip H. Karp
,
Douglas B. Hornick
,
Patrick L. Sinn
,
Anthony J. Fischer
,
Alejandro A. Pezzulo
,
Paul B. McCray
,
David K. Meyerholz
,
Joseph Zabner
,
Randall S. Prather
,
Michael J. Welsh
,
David A. Stoltz
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.05.22.594822
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.05.22.594822
Mutations in more than 50 different genes cause primary ciliary dyskinesia (PCD) by disrupting the activity of motile cilia that facilitate mucociliary transport (MCT). Knowledge of PCD has come from studies identifying disease-causing mutations, characterizing structural cilia abnormalities, finding genotype-phenotype relationships, and studying the cell biology of cilia. Despite these important findings, we still lack effective treatments and people with PCD have significant pulmonary impairment. As with many other diseases, a better understanding of pathogenic mechanisms may lead to effective treatments. To pursue disease mechanisms, we used CRISPR-Cas9 to develop a PCD pig with a disrupted DNAI1 gene. PCD pig airway cilia lacked the outer dynein arm and had impaired beating. MCT was impaired under both baseline conditions and after cholinergic stimulation in PCD pigs. Neonatal PCD pigs developed neonatal respiratory distress with evidence of atelectasis, air trapping, and airway mucus obstruction. Despite airway mucus accumulation, lung bacterial counts were similar between neonatal wild-type and PCD pigs. Sinonasal disease was present in all neonatal PCD pigs. Older PCD pigs developed worsening airway mucus obstruction, inflammation, and bacterial infection. This pig model closely mimics the disease phenotype seen in people with PCD and can be used to better understand the pathophysiology of PCD airway disease.
Related Topics
Concepts
Primary ciliary dyskinesia
Primary (astronomy)
Dyskinesia
Mutation
Genetics
Medicine
Biology
Internal medicine
Physics
Gene
Bronchiectasis
Astrophysics
Parkinson's disease
Lung
Disease
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.05.22.594822
- https://www.biorxiv.org/content/biorxiv/early/2024/05/26/2024.05.22.594822.full.pdf
- OA Status
- green
- References
- 64
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4399053222
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4399053222Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2024.05.22.594822Digital Object Identifier
- Title
-
Development and Initial Characterization of Pigs withDNAI1Mutations and Primary Ciliary DyskinesiaWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-05-26Full publication date if available
- Authors
-
Mahmoud H. Abou Alaiwa, B. Hilkin, Margaret P. Price, Nicholas D. Gansemer, Michael R. Rector, Mal R. Stroik, Linda S. Powers, Kristin M. Whitworth, Melissa Samuel, Akansha Jain, Lynda S. Ostedgaard, Sarah E. Ernst, Winter Philibert, Linda D. Boyken, Thomas O. Moninger, Phillip H. Karp, Douglas B. Hornick, Patrick L. Sinn, Anthony J. Fischer, Alejandro A. Pezzulo, Paul B. McCray, David K. Meyerholz, Joseph Zabner, Randall S. Prather, Michael J. Welsh, David A. StoltzList of authors in order
- Landing page
-
https://doi.org/10.1101/2024.05.22.594822Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2024/05/26/2024.05.22.594822.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2024/05/26/2024.05.22.594822.full.pdfDirect OA link when available
- Concepts
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Primary ciliary dyskinesia, Primary (astronomy), Dyskinesia, Mutation, Genetics, Medicine, Biology, Internal medicine, Physics, Gene, Bronchiectasis, Astrophysics, Parkinson's disease, Lung, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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64Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W3108590102, https://openalex.org/W12215523, https://openalex.org/W2142218173, https://openalex.org/W2955911721, https://openalex.org/W2808504398, https://openalex.org/W2101594367, https://openalex.org/W2016504972, https://openalex.org/W2337940600, https://openalex.org/W1967782180, https://openalex.org/W4320734247, https://openalex.org/W4396585664, https://openalex.org/W3192892064, https://openalex.org/W4310458813, https://openalex.org/W4205257352, https://openalex.org/W2980561001, https://openalex.org/W4210597059, https://openalex.org/W3085007210, https://openalex.org/W2593296415, https://openalex.org/W2148022231, https://openalex.org/W2886868706, https://openalex.org/W2121780565, https://openalex.org/W3000042757, https://openalex.org/W2991324231, https://openalex.org/W4393048223, https://openalex.org/W3176431702, https://openalex.org/W77445965, https://openalex.org/W2152976668, https://openalex.org/W2087326716, https://openalex.org/W2039462910, https://openalex.org/W2253068377, https://openalex.org/W2624837927, https://openalex.org/W2044380511, https://openalex.org/W2101026179, https://openalex.org/W2034960770, https://openalex.org/W2106699966, https://openalex.org/W2022192316, https://openalex.org/W2146133502, https://openalex.org/W3092321013, https://openalex.org/W2945567049, https://openalex.org/W2530771665, https://openalex.org/W2725322436, https://openalex.org/W2805610760, https://openalex.org/W2950941218, https://openalex.org/W2032019813, https://openalex.org/W3090529572, https://openalex.org/W2089942817, https://openalex.org/W4392231295, https://openalex.org/W1990179332, https://openalex.org/W3177478456, https://openalex.org/W2147585754, https://openalex.org/W2082254161, https://openalex.org/W1509342485, https://openalex.org/W4281729990, https://openalex.org/W3130390244, https://openalex.org/W2085645372, https://openalex.org/W4205840862, https://openalex.org/W2129639344, https://openalex.org/W2468613529, https://openalex.org/W2419559734, https://openalex.org/W2045817586, https://openalex.org/W4225320189, https://openalex.org/W2089214886, https://openalex.org/W4206770737, https://openalex.org/W2301131921 |
| referenced_works_count | 64 |
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