Very mild disease phenotype of congenic CftrTgH(neoim)Hgu cystic fibrosis mice
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.
Conclusions: 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.
Author: Balazs Toth, Martina Wilke, Frauke Stanke, Martina Dorsch, Silke Jansen, Dirk Wedekind, Nikoletta Charizopoulou, Alice Bot, Marion Burmester, Sabine Leonhard-Marek, Hugo R de Jonge, Hans-Juergen Hedrich, Gerhard Breves and Burkhard Tummler
Cred
Published on: 2008-04-09
Limited copyright is granted for you to use and/or republish any story on this site for
any legitimate media purpose as long as you reference 7thSpace and any source mentioned in the story above. Please
make sure to read our disclaimer prior to contacting 7thSpace Interactive. To contact our editors, visit our online helpdesk. If you wish submit your own press release, click here.
Social Bookmarking
Digg this! | Post to del.icio.us | Post to Furl | Add to Netscape | Add to Yahoo! | Rojo
|
|
