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Polygenetic analysis of CFTR gene expression in mammalian species: Could the rabbit lead to a accurate CF animal model?


Par Cyril - Posté le 17 avril 2014

TitrePolygenetic analysis of CFTR gene expression in mammalian species: Could the rabbit lead to a accurate CF animal model?
Type de publicationMiscellaneous
Nouvelles publications1997
AuteursVuillaumier S, Hinnrasky J, Lecointre G, Lapoumeroulie C, Koltenboeck B, Lehn P, Puchelle E, Denamur E
RésuméSeveral groups have generated mouse models for CF by disrupting the mouse CFTR gene or, more recently, by introducing the most common mutation found in human, the Delta F508 mutation, into the mouse CFTR gene. Although these animals display some phenotypic features of CF patients with prominent intestinal pathology, the pulmonary and pancreatic CF manifestations are not accurately replicated. These data are in correlation with the pattern of CFTR expression as well as with anatomical and physiological differences in man and rodent. In order to verify an animal species which could lead to a better CF model than the today murine models, the nucleotides sequences of the CFTR promoter region and available cDNA of eight mammalian species representing four different orders (Primates, Artiodactylia, Lagomorpha and Rodentia) were analysed. Promoter sequence comparisons yielded two deeply separated groups, one including man, non-human primates, cow, and rabbit, and the other including the rodents. Phylogenetic analyses of CFTR cDNA deeply separated the rabbit from the two members of its presumed sister order of Rodentia. This unexpected rabbit-rodent divergence is corroborated by airway surface epithelium analyses. These analyses, as well as anatomical and developmental data, suggest that the rabbit provides a suitable tool for gene transfer investigations, and once rabbit embryonic cells become available, could lead to a better CF model than the today murine models by CFTR gene targeting.