Very mild disease phenotype of congenic <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>cystic fibrosis mice
<p>Abstract</p> <p>Background</p> <p>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 generatin...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-04-01
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| Series: | BMC Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2156/9/28 |
| _version_ | 1811337044462403584 |
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| author | Leonhard-Marek Sabine Burmester Marion Bot Alice Charizopoulou Nikoletta Wedekind Dirk Jansen Silke Dorsch Martina Stanke Frauke Wilke Martina Tóth Balázs de Jonge Hugo R Hedrich Hans-Jürgen Breves Gerhard Tümmler Burkhard |
| author_facet | Leonhard-Marek Sabine Burmester Marion Bot Alice Charizopoulou Nikoletta Wedekind Dirk Jansen Silke Dorsch Martina Stanke Frauke Wilke Martina Tóth Balázs de Jonge Hugo R Hedrich Hans-Jürgen Breves Gerhard Tümmler Burkhard |
| author_sort | Leonhard-Marek Sabine |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>mouse model with a divergent genetic background (129/Sv, C57BL/6, HsdOla:MF1) two inbred mutant mouse strains CF/1-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>had been generated using strict brother × sister mating. CF/1-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>mice were fertile and showed normal growth and lifespan. In this work the <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>insertional mutation was backcrossed from CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>onto the inbred backgrounds C57BL/6J and DBA/2J generating congenic animals in order to clarify the differential impact of the <it>Cftr </it>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-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and wild type controls.</p> <p>Results</p> <p>Under the standardized housing conditions of the animal facility, the four mouse strains CF/1-<it>Cftr</it><sup><it>TgH(neoim)Hgu</it></sup>, CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu</it></sup>, D2.129P2(CF/3)-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and B6.129P2(CF/3)-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>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)-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>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.</p> <p>Conclusion</p> <p>The amelioration of the clinical features and of the basic defect that had emerged during the generation of CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>mice was retained in the congenic mice indicating that the <it>Cftr </it>linkage group or other loci shared between the inbred strains contain(s) the major modifier(s) of attenuation of cystic fibrosis symptoms.</p> |
| first_indexed | 2024-04-13T17:48:19Z |
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| id | doaj.art-e21588a5c0394e37afba411aa1084183 |
| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-04-13T17:48:19Z |
| publishDate | 2008-04-01 |
| publisher | BMC |
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| series | BMC Genetics |
| spelling | doaj.art-e21588a5c0394e37afba411aa10841832022-12-22T02:36:50ZengBMCBMC Genetics1471-21562008-04-01912810.1186/1471-2156-9-28Very mild disease phenotype of congenic <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>cystic fibrosis miceLeonhard-Marek SabineBurmester MarionBot AliceCharizopoulou NikolettaWedekind DirkJansen SilkeDorsch MartinaStanke FraukeWilke MartinaTóth Balázsde Jonge Hugo RHedrich Hans-JürgenBreves GerhardTümmler Burkhard<p>Abstract</p> <p>Background</p> <p>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 <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>mouse model with a divergent genetic background (129/Sv, C57BL/6, HsdOla:MF1) two inbred mutant mouse strains CF/1-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>had been generated using strict brother × sister mating. CF/1-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>mice were fertile and showed normal growth and lifespan. In this work the <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>insertional mutation was backcrossed from CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>onto the inbred backgrounds C57BL/6J and DBA/2J generating congenic animals in order to clarify the differential impact of the <it>Cftr </it>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-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and wild type controls.</p> <p>Results</p> <p>Under the standardized housing conditions of the animal facility, the four mouse strains CF/1-<it>Cftr</it><sup><it>TgH(neoim)Hgu</it></sup>, CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu</it></sup>, D2.129P2(CF/3)-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>and B6.129P2(CF/3)-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>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)-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>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.</p> <p>Conclusion</p> <p>The amelioration of the clinical features and of the basic defect that had emerged during the generation of CF/3-<it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>mice was retained in the congenic mice indicating that the <it>Cftr </it>linkage group or other loci shared between the inbred strains contain(s) the major modifier(s) of attenuation of cystic fibrosis symptoms.</p>http://www.biomedcentral.com/1471-2156/9/28 |
| spellingShingle | Leonhard-Marek Sabine Burmester Marion Bot Alice Charizopoulou Nikoletta Wedekind Dirk Jansen Silke Dorsch Martina Stanke Frauke Wilke Martina Tóth Balázs de Jonge Hugo R Hedrich Hans-Jürgen Breves Gerhard Tümmler Burkhard Very mild disease phenotype of congenic <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>cystic fibrosis mice BMC Genetics |
| title | Very mild disease phenotype of congenic <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>cystic fibrosis mice |
| title_full | Very mild disease phenotype of congenic <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>cystic fibrosis mice |
| title_fullStr | Very mild disease phenotype of congenic <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>cystic fibrosis mice |
| title_full_unstemmed | Very mild disease phenotype of congenic <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>cystic fibrosis mice |
| title_short | Very mild disease phenotype of congenic <it>Cftr</it><sup><it>TgH(neoim)Hgu </it></sup>cystic fibrosis mice |
| title_sort | very mild disease phenotype of congenic it cftr it sup it tgh neoim hgu it sup cystic fibrosis mice |
| url | http://www.biomedcentral.com/1471-2156/9/28 |
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