Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs

Christopher S. Rogers; David A. Stoltz; David K. Meyerholz; Lynda S. Ostedgaard; Tatiana Rokhlina; Peter J. Taft; Mark P. Rogan; Alejandro A. Pezzulo; Philip H. Karp; Omar A. Itani; Amanda C. Kabel; Christine L. Wohlford-Lenane; Greg J. Davis; Robert A. Hanfland; Tony L. Smith; Melissa Samuel; David Wax; Clifton N. Murphy; August Rieke; Kristin Whitworth; Aliye Uc; Timothy D. Starner; Kim A. Brogden; Joel Shilyansky; Paul B. McCray; Joseph Zabner; Randall S. Prather; Michael J. Welsh

doi:10.1126/science.1163600

Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs

Christopher S. Rogers, David A. Stoltz, David K. Meyerholz, Lynda S. Ostedgaard, Tatiana Rokhlina, Peter J. Taft, Mark P. Rogan, Alejandro A. Pezzulo, Philip H. Karp, Omar A. Itani, Amanda C. Kabel, Christine L. Wohlford-Lenane, Greg J. Davis, Robert A. Hanfland, Tony L. Smith, Melissa Samuel, David Wax, Clifton N. Murphy, August Rieke, Kristin WhitworthAliye Uc, Timothy D. Starner, Kim A. Brogden, Joel Shilyansky, Paul B. McCray, Joseph Zabner, Randall S. Prather, Michael J. Welsh

Division of Newborn Medicine

Research output: Contribution to journal › Article › peer-review

650 Scopus citations

Abstract

Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.

Original language	English
Pages (from-to)	1837-1841
Number of pages	5
Journal	Science
Volume	321
Issue number	5897
DOIs	https://doi.org/10.1126/science.1163600
State	Published - Sep 26 2008

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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., ... Welsh, M. J. (2008). Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science, 321(5897), 1837-1841. https://doi.org/10.1126/science.1163600

@article{72883c88381e4bdc92e8c7c9fa55ea7a,

title = "Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs",

abstract = "Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.",

author = "Rogers, {Christopher S.} and Stoltz, {David A.} and Meyerholz, {David K.} and Ostedgaard, {Lynda S.} and Tatiana Rokhlina and Taft, {Peter J.} and Rogan, {Mark P.} and Pezzulo, {Alejandro A.} and Karp, {Philip H.} and Itani, {Omar A.} and Kabel, {Amanda C.} and Wohlford-Lenane, {Christine L.} and Davis, {Greg J.} and Hanfland, {Robert A.} and Smith, {Tony L.} and Melissa Samuel and David Wax and Murphy, {Clifton N.} and August Rieke and Kristin Whitworth and Aliye Uc and Starner, {Timothy D.} and Brogden, {Kim A.} and Joel Shilyansky and McCray, {Paul B.} and Joseph Zabner and Prather, {Randall S.} and Welsh, {Michael J.}",

year = "2008",

month = sep,

day = "26",

doi = "10.1126/science.1163600",

language = "English",

volume = "321",

pages = "1837--1841",

journal = "Science",

issn = "0036-8075",

number = "5897",

}

Rogers, CS, Stoltz, DA, Meyerholz, DK, Ostedgaard, LS, Rokhlina, T, Taft, PJ, Rogan, MP, Pezzulo, AA, Karp, PH, Itani, OA, Kabel, AC, Wohlford-Lenane, CL, Davis, GJ, Hanfland, RA, Smith, TL, Samuel, M, Wax, D, Murphy, CN, Rieke, A, Whitworth, K, Uc, A, Starner, TD, Brogden, KA, Shilyansky, J, McCray, PB, Zabner, J, Prather, RS & Welsh, MJ 2008, 'Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs', Science, vol. 321, no. 5897, pp. 1837-1841. https://doi.org/10.1126/science.1163600

TY - JOUR

T1 - Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs

AU - Rogers, Christopher S.

AU - Stoltz, David A.

AU - Meyerholz, David K.

AU - Ostedgaard, Lynda S.

AU - Rokhlina, Tatiana

AU - Taft, Peter J.

AU - Rogan, Mark P.

AU - Pezzulo, Alejandro A.

AU - Karp, Philip H.

AU - Itani, Omar A.

AU - Kabel, Amanda C.

AU - Wohlford-Lenane, Christine L.

AU - Davis, Greg J.

AU - Hanfland, Robert A.

AU - Smith, Tony L.

AU - Samuel, Melissa

AU - Wax, David

AU - Murphy, Clifton N.

AU - Rieke, August

AU - Whitworth, Kristin

AU - Uc, Aliye

AU - Starner, Timothy D.

AU - Brogden, Kim A.

AU - Shilyansky, Joel

AU - McCray, Paul B.

AU - Zabner, Joseph

AU - Prather, Randall S.

AU - Welsh, Michael J.

PY - 2008/9/26

Y1 - 2008/9/26

N2 - Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.

AB - Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.

UR - http://www.scopus.com/inward/record.url?scp=52949154301&partnerID=8YFLogxK

U2 - 10.1126/science.1163600

DO - 10.1126/science.1163600

M3 - Article

C2 - 18818360

AN - SCOPUS:52949154301

SN - 0036-8075

VL - 321

SP - 1837

EP - 1841

JO - Science

JF - Science

IS - 5897

ER -

Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs

Abstract

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