OMIA 001794-9823 : Cystic fibrosis in Sus scrofa

See the equivalent entry at NCBI

In other species: domestic ferret

Possible human homologue (MIM number): 219700

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key mutation known: no

Species-specific description: Genetically-modifed organism; GMO.

This entry refers to a pig model of cystic fibrosis created by Rogers et al. (2008) by "adeno-associated virus-mediated [CFTR] gene targeting and somatic cell nuclear transfer", i.e. by knocking out and creating a mutant form of the CFTR gene in vitro, and then using the mutated cells to create cloned pigs. CFTR encodes the cystic fibrosis transmembrane conductance regulator. Mutations in CFTR cause cystic fibrosis in humans (see MIM entry above). Klymiuk et al. (2012) produced a similar clone of pigs with an inactivated CFTR via "sequential targeting using modified bacterial artificial chromosome vectors" followed by somatic cell nuclear transfer.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CFTR cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7) Sus scrofa 18 NC_010460.4 (28818209..28627717) CFTR Homologene, Ensembl, NCBI gene

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2016 Cooney, A.L., Abou Alaiwa, M.H., Shah, V.S., Bouzek, D.C., Stroik, M.R., Powers, L.S., Gansemer, N.D., Meyerholz, D.K., Welsh, M.J., Stoltz, D.A., Sinn, P.L., McCray, P.B. :
Lentiviral-mediated phenotypic correction of cystic fibrosis pigs. JCI Insight 1:, 2016. Pubmed reference: 27656681. DOI: 10.1172/jci.insight.88730.
Meyerholz, D.K. :
Lessons learned from the cystic fibrosis pig. Theriogenology 86:427-32, 2016. Pubmed reference: 27142487. DOI: 10.1016/j.theriogenology.2016.04.057.
Steines, B., Dickey, D.D., Bergen, J., Excoffon, K.J., Weinstein, J.R., Li, X., Yan, Z., Alaiwa, M.H., Shah, V.S., Bouzek, D.C., Powers, L.S., Gansemer, N.D., Ostedgaard, L.S., Engelhardt, J.F., Stoltz, D.A., Welsh, M.J., Sinn, P.L., Schaffer, D.V., Zabner, J. :
CFTR gene transfer with AAV improves early cystic fibrosis pig phenotypes. JCI Insight 1:e88728, 2016. Pubmed reference: 27699238. DOI: 10.1172/jci.insight.88728.
2013 Potash, A.E., Wallen, T.J., Karp, P.H., Ernst, S., Moninger, T.O., Gansemer, N.D., Stoltz, D.A., Zabner, J., Chang, E.H. :
Adenoviral Gene Transfer Corrects the Ion Transport Defect in the Sinus Epithelia of a Porcine CF Model. Mol Ther :, 2013. Pubmed reference: 23511247. DOI: 10.1038/mt.2013.49.
Reznikov, L.R., Dong, Q., Chen, J.H., Moninger, T.O., Park, J.M., Zhang, Y., Du, J., Hildebrand, M.S., Smith, R.J., Randak, C.O., Stoltz, D.A., Welsh, M.J. :
CFTR-deficient pigs display peripheral nervous system defects at birth. Proc Natl Acad Sci U S A 110:3083-8, 2013. Pubmed reference: 23382208. DOI: 10.1073/pnas.1222729110.
2012 Chang, E.H., Pezzulo, A.A., Meyerholz, D.K., Potash, A.E., Wallen, T.J., Reznikov, L.R., Sieren, J.C., Karp, P.H., Ernst, S., Moninger, T.O., Gansemer, N.D., McCray, P.B., Stoltz, D.A., Welsh, M.J., Zabner, J. :
Sinus hypoplasia precedes sinus infection in a porcine model of cystic fibrosis. Laryngoscope 122:1898-905, 2012. Pubmed reference: 22711071. DOI: 10.1002/lary.23392.
Klymiuk, N., Mundhenk, L., Kraehe, K., Wuensch, A., Plog, S., Emrich, D., Langenmayer, M.C., Stehr, M., Holzinger, A., Kröner, C., Richter, A., Kessler, B., Kurome, M., Eddicks, M., Nagashima, H., Heinritzi, K., Gruber, A.D., Wolf, E. :
Sequential targeting of CFTR by BAC vectors generates a novel pig model of cystic fibrosis. J Mol Med (Berl) 90:597-608, 2012. Pubmed reference: 22170306. DOI: 10.1007/s00109-011-0839-y.
Pezzulo, A.A., Tang, X.X., Hoegger, M.J., Alaiwa, M.H., Ramachandran, S., Moninger, T.O., Karp, P.H., Wohlford-Lenane, C.L., Haagsman, H.P., van Eijk, M., Bánfi, B., Horswill, A.R., Stoltz, D.A., McCray, P.B., Welsh, M.J., Zabner, J. :
Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature 487:109-13, 2012. Pubmed reference: 22763554. DOI: 10.1038/nature11130.
Potton, E. :
Reduced pH in the airways alters bacterial killing in CFTR-/- porcine lungs. Thorax :, 2012. Pubmed reference: 23125169. DOI: 10.1136/thoraxjnl-2012-202842.
Uc, A., Giriyappa, R., Meyerholz, D.K., Griffin, M., Ostedgaard, L.S., Tang, X.X., Abu-El-Haija, M., Stoltz, D.A., Ludwig, P., Pezzulo, A., Abu-El-Haija, M., Taft, P., Welsh, M.J. :
Pancreatic and biliary secretion are both altered in cystic fibrosis pigs. Am J Physiol Gastrointest Liver Physiol 303:G961-8, 2012. Pubmed reference: 22936270. DOI: 10.1152/ajpgi.00030.2012.
2011 Abu-El-Haija, M., Sinkora, M., Meyerholz, D.K., Welsh, M.J., McCray, P.B., Butler, J., Uc, A. :
An activated immune and inflammatory response targets the pancreas of newborn pigs with cystic fibrosis. Pancreatology 11:506-15, 2011. Pubmed reference: 22057257. DOI: 10.1159/000332582.
Chang, E.H., Lacruz, R.S., Bromage, T.G., Bringas, P., Welsh, M.J., Zabner, J., Paine, M.L. :
Enamel pathology resulting from loss of function in the cystic fibrosis transmembrane conductance regulator in a porcine animal model. Cells Tissues Organs 194:249-54, 2011. Pubmed reference: 21525720. DOI: 10.1159/000324248.
Cho, H.J., Joo, N.S., Wine, J.J. :
Defective fluid secretion from submucosal glands of nasal turbinates from CFTR-/- and CFTR (ΔF508/ΔF508) pigs. PLoS One 6:e24424, 2011. Pubmed reference: 21935358. DOI: 10.1371/journal.pone.0024424.
Fisher, J.T., Zhang, Y., Engelhardt, J.F. :
Comparative biology of cystic fibrosis animal models. Methods Mol Biol 742:311-34, 2011. Pubmed reference: 21547741. DOI: 10.1007/978-1-61779-120-8_19.
Keiser, N.W., Engelhardt, J.F. :
New animal models of cystic fibrosis: what are they teaching us? Curr Opin Pulm Med 17:478-83, 2011. Pubmed reference: 21857224. DOI: 10.1097/MCP.0b013e32834b14c9.
Ostedgaard, L.S., Meyerholz, D.K., Chen, J.H., Pezzulo, A.A., Karp, P.H., Rokhlina, T., Ernst, S.E., Hanfland, R.A., Reznikov, L.R., Ludwig, P.S., Rogan, M.P., Davis, G.J., Dohrn, C.L., Wohlford-Lenane, C., Taft, P.J., Rector, M.V., Hornick, E., Nassar, B.S., Samuel, M., Zhang, Y., Richter, S.S., Uc, A., Shilyansky, J., Prather, R.S., McCray, P.B., Zabner, J., Welsh, M.J., Stoltz, D.A. :
The ΔF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs. Sci Transl Med 3:74ra24, 2011. Pubmed reference: 21411740. DOI: 10.1126/scitranslmed.3001868.
Pierucci-Alves, F., Akoyev, V., Stewart, J.C., Wang, L.H., Janardhan, K.S., Schultz, B.D. :
Swine models of cystic fibrosis reveal male reproductive tract phenotype at birth. Biol Reprod 85:442-51, 2011. Pubmed reference: 21593481. DOI: 10.1095/biolreprod.111.090860.
2010 Joo, N.S., Cho, H.J., Khansaheb, M., Wine, J.J. :
Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs. J Clin Invest 120:3161-6, 2010. Pubmed reference: 20739758. DOI: 10.1172/JCI43466.
Li, H., Ganta, S., Fong, P. :
Altered ion transport by thyroid epithelia from CFTR(-/-) pigs suggests mechanisms for hypothyroidism in cystic fibrosis. Exp Physiol 95:1132-44, 2010. Pubmed reference: 20729267. DOI: 10.1113/expphysiol.2010.054700.
Meyerholz, D.K., Stoltz, D.A., Pezzulo, A.A., Welsh, M.J. :
Pathology of gastrointestinal organs in a porcine model of cystic fibrosis. Am J Pathol 176:1377-89, 2010. Pubmed reference: 20110417. DOI: 10.2353/ajpath.2010.090849.
Stoltz, D.A., Meyerholz, D.K., Pezzulo, A.A., Ramachandran, S., Rogan, M.P., Davis, G.J., Hanfland, R.A., Wohlford-Lenane, C., Dohrn, C.L., Bartlett, J.A., Nelson, G.A., Chang, E.H., Taft, P.J., Ludwig, P.S., Estin, M., Hornick, E.E., Launspach, J.L., Samuel, M., Rokhlina, T., Karp, P.H., Ostedgaard, L.S., Uc, A., Starner, T.D., Horswill, A.R., Brogden, K.A., Prather, R.S., Richter, S.S., Shilyansky, J., McCray, P.B., Zabner, J., Welsh, M.J. :
Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med 2:29ra31, 2010. Pubmed reference: 20427821. DOI: 10.1126/scitranslmed.3000928.
Widdicombe, J.H. :
Transgenic animals may help resolve a sticky situation in cystic fibrosis. J Clin Invest 120:3093-6, 2010. Pubmed reference: 20739746. DOI: 10.1172/JCI44235.
2009 Welsh, M.J., Rogers, C.S., Stoltz, D.A., Meyerholz, D.K., Prather, R.S. :
Development of a porcine model of cystic fibrosis. Trans Am Clin Climatol Assoc 120:149-62, 2009. Pubmed reference: 19768173.
2008 Liu, Y., Wang, Y., Jiang, Y., Zhu, N., Liang, H., Xu, L., Feng, X., Yang, H., Ma, T. :
Mild processing defect of porcine DeltaF508-CFTR suggests that DeltaF508 pigs may not develop cystic fibrosis disease. Biochem Biophys Res Commun 373:113-8, 2008. Pubmed reference: 18555011. DOI: 10.1016/j.bbrc.2008.06.009.
Rogers, C.S., Hao, Y., Rokhlina, T., Samuel, M., Stoltz, D.A., Li, Y., Petroff, E., Vermeer, D.W., Kabel, A.C., Yan, Z., Spate, L., Wax, D., Murphy, C.N., Rieke, A., Whitworth, K., Linville, M.L., Korte, S.W., Engelhardt, J.F., Welsh, M.J., Prather, R.S. :
Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. J Clin Invest 118:1571-7, 2008. Pubmed reference: 18324337. DOI: 10.1172/JCI34773.
Rogers, C.S., Stoltz, D.A., Meyerholz, D.K., Ostedgaard, L.S., Rokhlina, T., Taft, P.J., Rogan, M.P., Pezzulo, A.A., Karp, P.H., Itani, O.A., Kabel, A.C., Wohlford-Lenane, C.L., Davis, G.J., Hanfland, R.A., Smith, T.L., Samuel, M., Wax, D., Murphy, C.N., Rieke, A., Whitworth, K., Uc, A., Starner, T.D., Brogden, K.A., Shilyansky, J., McCray, P.B., Zabner, J., Prather, R.S., Welsh, M.J. :
Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321:1837-41, 2008. Pubmed reference: 18818360. DOI: 10.1126/science.1163600.

Edit History


  • Created by Frank Nicholas on 01 May 2013
  • Changed by Frank Nicholas on 01 May 2013
  • Changed by Frank Nicholas on 29 Sep 2016