Footprint-free mutations
• F508del
• G542X (1)
• G551D
• W1282X (11)
Conditional and revertible mutations
• Conditional (2)
• Revertible (3)
Exon replacement strains
• G542X exon 12 replacement. A segment of the human gene with G542X replaces the cognate mouse sequences. (121 bp of human CFTR intron 11, all 95 bp of exon 12 with G542X, and 84 bp of intron 12).
• R553X exon 12 replacement. A segment of the human gene with R553X replaces the cognate mouse sequences. (121 bp of human CFTR intron 11, all 95 bp of exon 12 with R553X, and 84 bp of intron 12).
• W1282X exon 23 replacement. A segment of the human gene with W1282X replaces the cognate mouse sequences. (207 bp of human CFTR intron 22, all 156 bp of exon 23 with W1282X, and 101 bp of intron 23).
• F508del exon 11 replacement. A segment of the human gene with F508del replaces the cognate mouse sequences. (148 bp of human CFTR intron 10, all 189 bp of exon 11 with F508del, and 83 bp of intron 11).
Human BAC transgenic mice
• B6-Tg(CFTR)1Lcl/Cwr (4) These mice carry a BAC transgene with the complete human CFTR gene including 40.1 kb upstream and 25kb downstream of CFTR. This is the wildtype version of this mouse and complements loss of mouse Cftr.
• B6-Tg(CFTRF508del)Cwr These mice have the F508del mutation created using endonuclease mediated gene editing in the mice in Gawenis et al., 20195 that carry a BAC transgene with the human CFTR gene.
• B6-Tg(CFTRG551D)Cwr – These mice have the G551D mutation created using endonuclease mediated gene editing in the mice in Gawenis et al., 20195 that carry a BAC transgene with the human CFTR gene.
Legacy strains
• Cftrtm1Unc (S489X mutation)- Snouwaert et al., 1992 (6) These mice have the S489X mutation and a neomycin cassette within exon 11.
• Cftrtm1Kth (F508del mutation)- Zehier et al., 1995 (7) These mice have the F508del mutation and a neomycin cassette insert between exon 11 and 12.
• Cftrtm2Mrc (R117H mutation)- van Heeckeren et al., 2004. (8) These mice have the R117H mutation in exon 4 and a neomycin cassette insert between exon 4 and 5.
• Cftrtm1KthTg(FABPCFTR)1Jaw/Cwr (gut corrected mice with F508del mutation)- crossed Zhou mutation with Cftrtm1Kth (9, 10) These mice have the F508del mutation but also express human Cftr from the fatty acid binding protein promoter (FABP). Since this allows for Cftr expression in the intestines, there is very little intestinal obstruction in these CF mice and have been labeled “gut-corrected”. However human CFTR may be expressed elsewhere in the mouse
Other Strains
• T-insertion null A T insertion in exon 11 created by gene editing
• Exon 11 deleted null (Cftrtm1.1Cwr)
• WT exon 11 replacement
• WT exon 12 replacement
• WT exon 23 replacement
References
1. McHugh DR, Steele MS, Valerio DM, Miron A, Mann RJ, LePage DF, Conlon RA, Cotton CU, Drumm ML, Hodges CA. A G542X cystic fibrosis mouse model for examining nonsense mutation directed therapies. PLoS One. 2018;13(6):e0199573. Epub 2018/06/21. doi: 10.1371/journal.pone.0199573. PubMed PMID: 29924856; PMCID: PMC6010256.
2. Hodges CA, Cotton CU, Palmert MR, Drumm ML. Generation of a conditional null allele for Cftr in mice. Genesis. 2008;46(10):546-52. Epub 2008/09/20. doi: 10.1002/dvg.20433. PubMed PMID: 18802965; PMCID: PMC2711445.
3. Hodges CA, Grady BR, Mishra K, Cotton CU, Drumm ML. Cystic fibrosis growth retardation is not correlated with loss of Cftr in the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2011;301(3):G528-36. Epub 2011/06/11. doi: 10.1152/ajpgi.00052.2011. PubMed PMID: 21659619; PMCID: PMC3174541.
4. Gawenis LR, Hodges, C.A., McHugh, D.R., Valerio, D.M., Miron, A., Cotton, C.U., Liu, J., Walker, N.M., Strubberg, A.M., Gillen, A.E., Mutolo, M.J., Kotzamanis, G., Harris, A., Drumm, M.L., Clarke, L.L. A BAC Transgenic Mouse Expression Human CFTR Under Control Of Its Regulatory Elements Rescues Cftr Knockout MIce. (in preparation). 2018.
5. Gawenis LR, Hodges CA, McHugh DR, Valerio DM, Miron A, Cotton CU, Liu J, Walker NM, Strubberg AM, Gillen AE, Mutolo MJ, Kotzamanis G, Bosch J, Harris A, Drumm ML, Clarke LL. A BAC Transgene Expressing Human CFTR under Control of Its Regulatory Elements Rescues Cftr Knockout Mice. Sci Rep. 2019;9(1):11828. doi: 10.1038/s41598-019-48105-4. PubMed PMID: 31413336; PMCID: PMC6694137.
6. Snouwaert JN, Brigman KK, Latour AM, Malouf NN, Boucher RC, Smithies O, Koller BH. An animal model for cystic fibrosis made by gene targeting. Science. 1992;257(5073):1083-8. PubMed PMID: 1380723.
7. Zeiher BG, Eichwald E, Zabner J, Smith JJ, Puga AP, McCray PB, Jr., Capecchi MR, Welsh MJ, Thomas KR. A mouse model for the delta F508 allele of cystic fibrosis. J Clin Invest. 1995;96(4):2051-64. Epub 1995/10/01. doi: 10.1172/JCI118253. PubMed PMID: 7560099; PMCID: PMC185844.
8. van Heeckeren AM, Schluchter MD, Drumm ML, Davis PB. Role of Cftr genotype in the response to chronic Pseudomonas aeruginosa lung infection in mice. Am J Physiol Lung Cell Mol Physiol. 2004;287(5):L944-52. Epub 2004/07/13. doi: 10.1152/ajplung.00387.2003. PubMed PMID: 15246977.
9. Darrah RJ, Bederman IR, Mitchell AL, Hodges CA, Campanaro CK, Drumm ML, Jacono FJ. Ventilatory pattern and energy expenditure are altered in cystic fibrosis mice. J Cyst Fibros. 2013;12(4):345-51. Epub 2013/01/08. doi: 10.1016/j.jcf.2012.11.008. PubMed PMID: 23290341; PMCID: PMC3620718.
10. Zhou L, Dey CR, Wert SE, DuVall MD, Frizzell RA, Whitsett JA. Correction of lethal intestinal defect in a mouse model of cystic fibrosis by human CFTR. Science. 1994;266(5191):1705-8. PubMed PMID: 7527588.
11. Michicich M, Traylor Z, McCoy C, Valerio DM, Wilson A, Schneider M, Davis S, Barabas A, Mann RJ, LePage DF, Jiang W, Drumm ML, Kelley TJ, Conlon RA, Hodges CA. A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function. J Cyst Fibros. 2024 Nov 11:S1569-1993(24)01797-1. doi: 10.1016/j.jcf.2024.10.008. PMID: 39532588.
1. McHugh DR, Steele MS, Valerio DM, Miron A, Mann RJ, LePage DF, Conlon RA, Cotton CU, Drumm ML, Hodges CA. A G542X cystic fibrosis mouse model for examining nonsense mutation directed therapies. PLoS One. 2018;13(6):e0199573. Epub 2018/06/21. doi: 10.1371/journal.pone.0199573. PubMed PMID: 29924856; PMCID: PMC6010256.
2. Hodges CA, Cotton CU, Palmert MR, Drumm ML. Generation of a conditional null allele for Cftr in mice. Genesis. 2008;46(10):546-52. Epub 2008/09/20. doi: 10.1002/dvg.20433. PubMed PMID: 18802965; PMCID: PMC2711445.
3. Hodges CA, Grady BR, Mishra K, Cotton CU, Drumm ML. Cystic fibrosis growth retardation is not correlated with loss of Cftr in the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2011;301(3):G528-36. Epub 2011/06/11. doi: 10.1152/ajpgi.00052.2011. PubMed PMID: 21659619; PMCID: PMC3174541.
4. Gawenis LR, Hodges, C.A., McHugh, D.R., Valerio, D.M., Miron, A., Cotton, C.U., Liu, J., Walker, N.M., Strubberg, A.M., Gillen, A.E., Mutolo, M.J., Kotzamanis, G., Harris, A., Drumm, M.L., Clarke, L.L. A BAC Transgenic Mouse Expression Human CFTR Under Control Of Its Regulatory Elements Rescues Cftr Knockout MIce. (in preparation). 2018.
5. Gawenis LR, Hodges CA, McHugh DR, Valerio DM, Miron A, Cotton CU, Liu J, Walker NM, Strubberg AM, Gillen AE, Mutolo MJ, Kotzamanis G, Bosch J, Harris A, Drumm ML, Clarke LL. A BAC Transgene Expressing Human CFTR under Control of Its Regulatory Elements Rescues Cftr Knockout Mice. Sci Rep. 2019;9(1):11828. doi: 10.1038/s41598-019-48105-4. PubMed PMID: 31413336; PMCID: PMC6694137.
6. Snouwaert JN, Brigman KK, Latour AM, Malouf NN, Boucher RC, Smithies O, Koller BH. An animal model for cystic fibrosis made by gene targeting. Science. 1992;257(5073):1083-8. PubMed PMID: 1380723.
7. Zeiher BG, Eichwald E, Zabner J, Smith JJ, Puga AP, McCray PB, Jr., Capecchi MR, Welsh MJ, Thomas KR. A mouse model for the delta F508 allele of cystic fibrosis. J Clin Invest. 1995;96(4):2051-64. Epub 1995/10/01. doi: 10.1172/JCI118253. PubMed PMID: 7560099; PMCID: PMC185844.
8. van Heeckeren AM, Schluchter MD, Drumm ML, Davis PB. Role of Cftr genotype in the response to chronic Pseudomonas aeruginosa lung infection in mice. Am J Physiol Lung Cell Mol Physiol. 2004;287(5):L944-52. Epub 2004/07/13. doi: 10.1152/ajplung.00387.2003. PubMed PMID: 15246977.
9. Darrah RJ, Bederman IR, Mitchell AL, Hodges CA, Campanaro CK, Drumm ML, Jacono FJ. Ventilatory pattern and energy expenditure are altered in cystic fibrosis mice. J Cyst Fibros. 2013;12(4):345-51. Epub 2013/01/08. doi: 10.1016/j.jcf.2012.11.008. PubMed PMID: 23290341; PMCID: PMC3620718.
10. Zhou L, Dey CR, Wert SE, DuVall MD, Frizzell RA, Whitsett JA. Correction of lethal intestinal defect in a mouse model of cystic fibrosis by human CFTR. Science. 1994;266(5191):1705-8. PubMed PMID: 7527588.
11. Michicich M, Traylor Z, McCoy C, Valerio DM, Wilson A, Schneider M, Davis S, Barabas A, Mann RJ, LePage DF, Jiang W, Drumm ML, Kelley TJ, Conlon RA, Hodges CA. A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function. J Cyst Fibros. 2024 Nov 11:S1569-1993(24)01797-1. doi: 10.1016/j.jcf.2024.10.008. PMID: 39532588.
All mice are on the C57Bl/6J inbred background.