Evaluation of gene targeting by homologous recombination in ovine somatic cells

Williams, S. Henry; Sahota, Virender K.; Pálmai-Pallag, Timea; Tebbutt, Scott J.; Walker, J.-A.; Harris, Ann

doi:10.1002/mrd.10340

Cited by 20 publications

(20 citation statements)

References 36 publications

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“…So far, only mice have been successfully used in modelling by homologous recombination and transgenesis. Despite intensive efforts, CF sheep (Williams et al 2003) or ferrets (Li & Engelhardt 2003) have not been created but may become a valuable contribution to studies of CF in animals and chronic lung disease applicable to human diseases.…”

Section: Other Animal Modelsmentioning

confidence: 99%

Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

Kukavica-Ibrulj

Levesque

2008

Lab Anim

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SummaryCystic fibrosis (CF) is caused by a defect in the transmembrane conductance regulator (CFTR) protein that functions as a chloride channel. Dysfunction of the CFTR protein results in salty sweat, pancreatic insufficiency, intestinal obstruction, male infertility and severe pulmonary disease. In most patients with CF life expectancy is limited due to a progressive loss of functional lung tissue. Early in life a persistent neutrophylic inflammation can be demonstrated in the airways. The cause of this inflammation, the role of CFTR and the cause of lung morbidity by different CF-specific bacteria, mostly Pseudomonas aeruginosa, are not well understood. The lack of an appropriate animal model with multi-organ pathology having the characteristics of the human form of CF has hampered our understanding of the pathobiology and chronic lung infections of the disease for many years. This review summarizes the main characteristics of CF and focuses on several available animal models that have been frequently used in CF research. A better understanding of the chronic lung infection caused particularly by P. aeruginosa, the pathophysiology of lung inflammation and the pathogenesis of lung disease necessitates animal models to understand CF, and to develop and improve treatment.

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Section: Other Animal Modelsmentioning

confidence: 99%

Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

Kukavica-Ibrulj

Levesque

2008

Lab Anim

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“…So far, only mice have been successfully used in modelling by homologous recombination and transgenesis. Despite intensive efforts, CF sheep [79] or ferrets [80] have not been created but may become a valuable contribution to the field in the future.…”

Section: Other Animal Modelsmentioning

confidence: 99%

Animal models of cystic fibrosis

Scholte

Davidson

Wilke

et al. 2004

Journal of Cystic Fibrosis

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“…Unlike mouse ES cells, classical homologous recombination in somatic cells results in extremely low gene targeting efficiencies (17,18). Homologous recombination strategies often employ a promoter-trap strategy that improves gene targeting efficiency by decreasing the number of random integration events.…”

Section: Introductionmentioning

confidence: 99%

Production of CFTR-null and CFTR-ΔF508 heterozygous pigs by adeno-associated virus–mediated gene targeting and somatic cell nuclear transfer

et al. 2008

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Progress toward understanding the pathogenesis of cystic fibrosis (CF) and developing effective therapies has been hampered by lack of a relevant animal model. CF mice fail to develop the lung and pancreatic disease that cause most of the morbidity and mortality in patients with CF. Pigs may be better animals than mice in which to model human genetic diseases because their anatomy, biochemistry, physiology, size, and genetics are more similar to those of humans. However, to date, gene-targeted mammalian models of human genetic disease have not been reported for any species other than mice. Here we describe the first steps toward the generation of a pig model of CF. We used recombinant adeno-associated virus (rAAV) vectors to deliver genetic constructs targeting the CF transmembrane conductance receptor (CFTR) gene to pig fetal fibroblasts. We generated cells with the CFTR gene either disrupted or containing the most common CF-associated mutation (ΔF508). These cells were used as nuclear donors for somatic cell nuclear transfer to porcine oocytes. We thereby generated heterozygote male piglets with each mutation. These pigs should be of value in producing new models of CF. In addition, because gene-modified mice often fail to replicate human diseases, this approach could be used to generate models of other human genetic diseases in species other than mice.

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Evaluation of gene targeting by homologous recombination in ovine somatic cells

Cited by 20 publications

References 36 publications

Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

Animal models of cystic fibrosis

Production of CFTR-null and CFTR-ΔF508 heterozygous pigs by adeno-associated virus–mediated gene targeting and somatic cell nuclear transfer

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