TITLE

Very mild disease phenotype of congenic CftrTgH(neoim)Hgu cystic fibrosis mice

AUTHOR(S)
Tóth, Balázs; Wilke, Martina; Stanke, Frauke; Dorsch, Martina; Jansen, Silke; Wedekind, Dirk; Charizopoulou, Nikoletta; Bot, Alice; Burmester, Marion; Leonhard-Marek, Sabine; de Jonge, Hugo R.; Hedrich, Hans-Jürgen; Breves, Gerhard; Tümmler, Burkhard
PUB. DATE
January 2008
SOURCE
BMC Genetics;2008, Vol. 9, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: A major boost to cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search for modifier genes. From the original CftrTgH(neoim)Hgu mouse model with a divergent genetic background (129/Sv, C57BL/6, HsdOla:MF1) two inbred mutant mouse strains CF/1-CftrTgH(neoim)Hgu and CF/3-CftrTgH(neoim)Hgu had been generated using strict brother x sister mating. CF/1-CftrTgH(neoim)Hgu and CF/3-CftrTgH(neoim)Hgu mice were fertile and showed normal growth and lifespan. In this work the CftrTgH(neoim)Hgu insertional mutation was backcrossed from CF/3-CftrTgH(neoim)Hgu onto the inbred backgrounds C57BL/6J and DBA/2J generating congenic animals in order to clarify the differential impact of the Cftr mutation and the genetic background on the disease phenotype of the cystic fibrosis mutant mice. Clinical and electrophysiological features of the two congenic strains were compared with those of CF/1-CftrTgH(neoim)Hgu and CF/3-CftrTgH(neoim)Hgu and wild type controls. Results: Under the standardized housing conditions of the animal facility, the four mouse strains CF/1-CftrTgH(neoim)Hgu, CF/3-CftrTgH(neoim)Hgu, D2.129P2(CF/3)-CftrTgH(neoim)Hgu and B6.129P2(CF/3)-CftrTgH(neoim)Hgu exhibited normal life expectancy. Growth of congenic cystic fibrosis mice was comparable with that of wild type controls. All mice but D2.129P2(CF/3)-CftrTgH(neoim)Hgu females were fertile. Short circuit current measurements revealed characteristic response profiles of the HsdOla:MF1, DBA/2J and C57BL/6J backgrounds in nose, ileum and colon. All cystic fibrosis mouse lines showed the disease-typical hyperresponsiveness to amiloride in the respiratory epithelium. The mean chloride secretory responses to carbachol or forskolin were 15-100% of those of the cognate wild type control animals. Conclusion: The amelioration of the clinical features and of the basic defect that had emerged during the generation of CF/3-CftrTgH(neoim)Hgu mice was retained in the congenic mice indicating that the Cftr linkage group or other loci shared between the inbred strains contain(s) the major modifier(s) of attenuation of cystic fibrosis symptoms.
ACCESSION #
36086225

 

Related Articles

  • A knockout mouse resource for the biomedical research community. Lloyd, K. C. Kent // Annals of the New York Academy of Sciences;Dec2011, Vol. 1245 Issue 1, p24 

    The Knockout Mouse Project (KOMP) Repository archives and distributes vectors, embryonic stem cell clones, frozen germplasm, and live mutant mice for 8,500 knockout genes. Here, we describe the creation and functions of the KOMP Repository.

  • Molecular models of the open and closed states of the whole human CFTR protein. Mornon, Jean-Paul; Lehn, Pierre; Callebaut, Isabelle // Cellular & Molecular Life Sciences;Nov2009, Vol. 66 Issue 21, p3469 

    Cystic fibrosis transmembrane conductance regulator (CFTR), involved in cystic fibrosis (CF), is a chloride channel belonging to the ATP-binding cassette (ABC) superfamily. Using the experimental structure of Sav1866 as template, we previously modeled the human CFTR structure, including...

  • Low Frequency of the ΔF508 Mutation of the CFTR Gene in a Highly Admixed Population in Bahia, Brazil. Moura Costa, Fabiana Maia; Santana, Maria Angélica; Moreira Lemos, Antônio Carlos; Galvão-Castro, Bernardo; Acosta, Angelina Xavier // Human Biology;Jun2007, Vol. 79 Issue 3, p293 

    Cystic fibrosis (CF) is the most common autosomal recessive disease in the European (Caucasian) population, with an incidence of 1:2,000 to 1:8,000. The ΔF508 mutation (66%) is predominant among more than 1,300 different mutations of the CFTR gene. The population of the state of Bahia, in...

  • Synergistic Post-Transcriptional Regulation of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) by miR-101 and miR-494 Specific Binding. Megiorni, Francesca; Cialfi, Samantha; Dominici, Carlo; Quattrucci, Serena; Pizzuti, Antonio // PLoS ONE;2011, Vol. 6 Issue 10, p1 

    microRNAs (miRNAs) are a class of regulatory small non-coding molecules that control gene expression at posttranscriptional level. Deregulation of miRNA functions affects a variety of biological processes also involved in the etiology of several human mendelian and complex diseases. Recently,...

  • Promising Insights into Cystic Fibrosis. Bone, Kerry // Townsend Letter for Doctors & Patients;Apr2005, Issue 261, p46 

    Comments on an article concerning cystic fibrosis. Characteristics of cystic fibrosis as a genetic disease frequently seen in Caucasian people caused by mutations in the cystic fibrosis transmembrane conductance regulator gene; Clinical symptoms; Effectiveness of drugs and existing treatments.

  • Analysis of 31 CFTR mutations by polymerase chain reaction/oligonucleotide ligation assay in a pilot screening of 4476 newborns for cystic fibrosis. Gasparini, P.; Arbustini, E.; Restagno, G.; Zelante, L.; Stanziale, P.; Gatta, L.; Sbaiz, L.; Sedita, A. M.; Banchieri, N.; Sapone, L.; Fiorucci, G. C.; Brinson, E.; Shulse, E.; Rappaport, E.; Fortina, P. // Journal of Medical Screening;Jun1999, Vol. 6 Issue 2, p67 

    Objectives Molecular biological testing for genetic diseases has grown rapidly, but speed, accuracy, specificity, sensitivity, throughput, and cost become more important as large scale screening is considered. This is a pilot study of an assay for the simultaneous detection of up to 31 cystic...

  • Cystic fibrosis with homozygous R553X mutation in a Taiwanese child. Hui-Ju Chen; Shuan-Pei Lin; Hung-Chang Lee; Chih-Ping Chen; Nan-Chang Chiu; Han-Yang Hung; Schu-Rern Chern; Chih-Kuang Chuang // Journal of Human Genetics;Dec2005, Vol. 50 Issue 12, p674 

    It has been reported that cystic fibrosis is very rare in Asians, and its clinical expression and genetic mutations are different from those found in Caucasians. We report the case of a boy who had chronic diarrhea with failure to thrive and frequent respiratory tract infections beginning at the...

  • Characterization of 19 disease-associated missense mutations in the regulatory domain of the cystic fibrosis transmembrane conductance regulator. Vankeerberghen, Anne; Wei, Lin; Jaspers, Martine; Cassiman, Jean‐Jacques; Nilius, Bernd; Cuppens, Harry // Human Molecular Genetics;Nov98, Vol. 7 Issue 11, p1761 

    Studies 19 disease-associated missense mutations in the regulatory domain of the cystic fibrosis transmembrane conductance regulator. Clustering of mutations in the N-terminal part of the regulatory domain; Mutants that induced a whole cell current.

  • Frequency of large CFTR gene rearrangements in Italian CF patients. Bombieri, Cristina; Bonizzato, Alberto; Castellani, Carlo; Assael, Baroukh M.; Pignatti, Pier Franco // European Journal of Human Genetics;May2005, Vol. 13 Issue 5, p687 

    In most populations, an appreciable fraction of cystic fibrosis transmembrane regulator (CFTR) gene mutations in patients affected by cystic fibrosis (CF) cannot be identified, and large gene rearrangements might be missed by standard analyses. We have searched large gene rearrangements in a...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics