ABCMdb

PMID: 18782827

Kukavica-Ibrulj I, Levesque RC
Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies.
Lab Anim. 2008 Oct;42(4):389-412. Epub 2008 Sep 9., [PubMed]

Sentences

No. Mutations Sentence Comment

142 ABCC7 p.Gly551Asp Several CF mouse models have been generated using gene targeting to disrupt the murine CFTR locus by homologous recombination (Dorin et al. 1992, Snouwaert et al. 1992, O`Neal et al. 1993, Ratcliff et al. 1993, Hasty et al. 1995, Rozmahel et al. 1996) and by introducing specific human mutations into the equivalent mouse loci, including DF508 (Colledge et al. 1995, van Doorninck et al. 1995, Zeiher et al. 1995, French et al. 1996) and the G551D mutation (Delaney et al. 1996, Dickinson et al. 2000). Login to comment 163 ABCC7 p.Gly551Asp ABCC7 p.Gly480Cys To address this question, a collection of recombinant CF mouse models was generated containing clinically relevant mutations in CFTR by introducing specific human mutations into the equivalent mouse loci including DF508 (Colledge et al. 1995, van Doorninck et al. 1995, Zeiher et al. 1995, French et al. 1996), G551D (substitution of a glycine with an aspartic acid) (Delaney et al. 1996) and G480C (missense mutation) (Dickinson et al. 2000) (Table 2). Login to comment 167 ABCC7 p.Gly542* Finally, a transgenic KO model expressing a human CFTR with the G542X mutation under the control of the intestinal fatty-acid-binding protein (FABP) gene promoter has been generated and used to study the effect of aminoglycosides on suppression of this CFTR premature stop mutation (Du et al. 2002). Login to comment 170 ABCC7 p.Gly551Asp ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Ser489* ABCC7 p.Gly480Cys Table 2 Cystic fibrosis (CF) mouse models CF mice Mutation/molecular strategy Phenotype/limitation CFTR KO CFTRtm1Unc (Snouwaert et al. 1992) Exon 10 replacement, null mutation, inframe stop Severe intestinal phenotype and high mortality; no lung disease CFTRtm1Hgu (Dorin et al. 1992) Exon 10 insertional mutagenesis Intestinal blockage; minor pathology in lungs of one mouse CFTRtm1Cam (Ratcliff et al. 1993) Exon 10 replacement, null mutation Severe intestinal phenotype and high mortality; pathology in lacrimal gland and pancreas of some mice; no lung disease CFTRtm1Bay (O`Neal et al. 1993) Exon 3 insertional duplication, null mutation Severe intestinal phenotype and high mortality; no lung disease CFTRtm1Hsc (Rozmahel et al. 1996) Exon 1 replacement, null mutation Severe intestinal phenotype and high mortality; no lung disease Other mutations CFTRtm1Kth (Zeiher et al. 1995) DF508 by exon 10 replacement High mortality and reduction in size, variable pathology of the gastrointestinal tract, normal lung, pancreas, gallbladder, male reproductive tract, lacrimal gland and submandibular glands CFTRtm1Eur (van Doorninck et al. 1995, French et al. 1996) DF508 by exon 10 'hit and run` Normal survival, growth retarded but no abnormalities or stasis of inspissated mucus in lungs, pancreas, liver bile ducts, vas deferens and salivary glands CFTRtm1G551D (Delaney et al. 1996) G551D by exon 11 replacement Moderate phenotype with reduced incidence of intestinal blockage and 67% survival; no lung disease CFTRtm2Hgu (Dickinson et al. 2000) G480C by exon 10 'hit and run` Normal survival, no reduction in body weight, preserved cAMP-mediated Cl2 response, decreased Ca2þ -related Cl2 response CFTR2/2hCFTR-G542X (Du et al. 2002) CFTR2/2 null mutation that also express a human CFTR-G542X stop mutation under control of the intestinal FABP promoter Suppression of the hCFTR-G542X mutation in vivo by aminoglycosides CFTRtm1Unc -TgN(FABPCFTR) (Zhou et al. 1994) Stop codon in the murine CFTR gene (S489X) but also express human CFTR in the gut epithelium (transgenic introduction of CFTR under FABP promoter) Functional correction of ileal goblet cell and crypt cell hyperplasia and cyclic adenosine monophosphate-stimulated chloride secretion, improved survival Congenic C57BL/6J CFTR2/2 (Durie et al. 2004) Long-lived congenic C57BL/6J CFTR2/2 All organs pathologically affected by the human form of CF Scnn1a-, Scnn1b- and Scnn1c-transgenic mice (Mall et al. 2004) Transgenic mice overexpressing airway-specific ENaC to increase Naþ absorption CF-like lung disease FABP: fatty acid-binding protein, ENaC: epithelial Naþ channels. Login to comment