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Phenotypic Characterization and Comparison of Cystic Fibrosis Rat Models Generated Using CRISPR/Cas9 Gene Editing.
McCarron, Alexandra; Cmielewski, Patricia; Reyne, Nicole; McIntyre, Chantelle; Finnie, John; Craig, Fiona; Rout-Pitt, Nathan; Delhove, Juliette; Schjenken, John E; Chan, Hon Y; Boog, Bernadette; Knight, Emma; Gilmore, Rodney C; O'Neal, Wanda K; Boucher, Richard C; Parsons, David; Donnelley, Martin.
Afiliación
  • McCarron A; Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Cmielewski P; Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Reyne N; Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • McIntyre C; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, North Adelaide, South Australia, Australia.
  • Finnie J; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Division of Anatomical Pathology, SA Pathology, Adelaide, South Australia, Australia.
  • Craig F; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, North Adelaide, South Australia, Australia.
  • Rout-Pitt N; Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Delhove J; Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Schjenken JE; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Chan HY; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Boog B; Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Knight E; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Gilmore RC; Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
  • O'Neal WK; Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
  • Boucher RC; Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
  • Parsons D; Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • Donnelley M; Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
Am J Pathol ; 190(5): 977-993, 2020 05.
Article en En | MEDLINE | ID: mdl-32084371
ABSTRACT
Animal models of cystic fibrosis (CF) are essential for investigating disease mechanisms and trialing potential therapeutics. This study generated two CF rat models using clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 gene editing. One rat model carries the common human Phe508del (ΔF508) CF transmembrane conductance regulator (CFTR) mutation, whereas the second is a CFTR knockout model. Phenotype was characterized using a range of functional and histologic assessments, including nasal potential difference to measure electrophysiological function in the upper airways, RNAscope in situ hybridization and quantitative PCR to assess CFTR mRNA expression in the lungs, immunohistochemistry to localize CFTR protein in the airways, and histopathologic assessments in a range of tissues. Both rat models revealed a range of CF manifestations, including reduced survival, intestinal obstruction, bioelectric defects in the nasal epithelium, histopathologic changes in the trachea, large intestine, and pancreas, and abnormalities in the development of the male reproductive tract. The CF rat models presented herein will prove useful for longitudinal assessments of pathophysiology and therapeutics.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Regulador de Conductancia de Transmembrana de Fibrosis Quística / Fibrosis Quística / Modelos Animales de Enfermedad / Edición Génica Límite: Animals / Humans Idioma: En Revista: Am J Pathol Año: 2020 Tipo del documento: Article País de afiliación: Australia
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Regulador de Conductancia de Transmembrana de Fibrosis Quística / Fibrosis Quística / Modelos Animales de Enfermedad / Edición Génica Límite: Animals / Humans Idioma: En Revista: Am J Pathol Año: 2020 Tipo del documento: Article País de afiliación: Australia