Cystic Fibrosis 
Mouse Models
Origin
Type
Background
Phenotype
Reference:
UNC  Knockout outbred severe intestinal disease Snouwaert et al.
Edinburgh Partial knockout Mixed? v. mild Dorin et al.
Cambridge Knockout Mixed? Severe Ratcliff et al.
Baylor Knockout C57BL Severe O'Neal et al.
Baylor Knockout   Severe Hasty et al.
Cambridge D F508   Severe Colledge et al.
Utah D F508 C57BL Severe Zeiher et al.
Rotterdam D F508   Severe van Doorninck
Brisbane G551D   Less severe intestinal block Delaney et al.
Toronto Knockout C57BL/6J  Severe, + lung disease Kent et al.
 Toronto  Knockout several  varied by background  Rozmahel et al. 
         

Snouwaert JN, Brigman KK, Latour AM, et al. An animal model for cystic fibrosis made by gene targeting. Science 1992;257:1083-1088.

Dorin JR, Dickinson P, Emslie E, et al. Successful targeting of the mouse cystic fibrosis transmembrane conductance regulator gene in embryonal stem cells. Transgenic Res 1992;1:101-105.

Ratcliff R, Evans MJ, Cuthbert AW, et al. Production of a severe cystic fibrosis mutation in mice by gene targeting. Nat Genet 1993;4:35-41.

O'Neal W, Hasty P, McCray PB, Jr., et al. A severe phenotype in mice with a duplication of exon 3 in the cystic fibrosis locus. Hum Mol Genet 1993;2:1561-1569.

Hasty P, WK ON, Liu KQ, et al. Severe phenotype in mice with termination mutation in exon 2 of cystic fibrosis gene. Somat Cell Mol Genet 1995;21:177-187.

Colledge WH, Abella BS, Southern KW, et al. Generation and characterization of a delta F508 cystic fibrosis mouse model. Nat Genet 1995;10:445-452.

Zeiher BG, Eichwald E, Zabner J, et al. A mouse model for the delta F508 allele of cystic fibrosis. J Clin Invest 1995;96:2051-2064.

van Doorninck JH, French PJ, Verbeek E, et al. A mouse model for the cystic fibrosis delta F508 mutation. Embo J 1995;14:4403-4411.

Delaney SJ, Alton EW, Smith SN, et al. Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype-phenotype correlations. Embo J 1996;15:955-963.Centre for Molecular and Cellular Biology, University of Queensland, Brisbane, Australia

Kent G, Iles R, Bear CE, et al. Lung Disease in Mice with Cystic Fibrosis. J Clin Invest 1997;100:3060-3069.

Rozmahel, R., M. Wilschanski, A. Matin, S. Plyte, M. Oliver, W. Auerbach, A. Moore, J. Forstner, P. Durie, J. Nadeau,
    et al (1996) Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a
    secondary genetic factor. Nat. Genet. 12: 280-287 [Medline]

A great advantage made possible by the cloning of the CF gene has been the ability to use gene targeting to "knock out" the cf gene in mice, or to produce mice homozygous for the D F508-CFTR mutation or G551D mutation . The phenotypes of these mice are examined closely in later chapters. For now, two generalizations seem to hold. First, if a small amount of natural CFTR escapes the targeted disruption, the mice are almost normal , and second, there is very little difference so far between null mice and mice with the D F508-CFTR mutation. Finally, and of great interest, is the finding that mice bred into certain backgrounds actually develop lung disease. 


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