ABCMdb

PMID: 7533607

Snouwaert JN, Brigman KK, Latour AM, Iraj E, Schwab U, Gilmour MI, Koller BH
A murine model of cystic fibrosis.
Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 2):S59-64., [PubMed]

Sentences

No. Mutations Sentence Comment

33 ABCC7 p.Ser489* The resulting mutation, which we have designated S489X, should result in a truncated gene product similar to that 560 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 151 1995 seen with several types of human CF mutations. Login to comment 36 ABCC7 p.Ser489* Once cell lines carrying the S489X mutation were isolated, they were used to generate mice carrying the same mutation. Login to comment 37 ABCC7 p.Ser489* This was accomplished by injecting the cells carrying the S489X mutation into mouse blastocysts and introducing the injected blastocysts into the uterus of a pseudopregnant female. Login to comment 39 ABCC7 p.Ser489* These animals were therefore able to pass the ES cell genome, including the S489X mutation, on to their offspring. Login to comment 40 ABCC7 p.Ser489* Offspring receiving the ES cell genome from one chimeric parent were initially identified based on coat color, and those heterozygous for he S489X mutation were subsequently identified by PCR analysis of tail DNA. Login to comment 46 ABCC7 p.Ser489* ABCC7 p.Ser489* RESULTS Survival We reported previously that genetic analysis of the offspring of CFTR(-I-) mice indicated that there was no prenatal mortality associated with the S489X mutation, because the ratio of offspring lacking the S489X mutation to those heterozygous or homozygous for the mutation did not deviate significantly from the expected Mendelian ratio of 1:2:1. Login to comment 82 ABCC7 p.Ser489* Another possibility is that the S489X mutation, because it results in a truncated CFTR protein, may result in more severe intestinal complications than the ..1.508 mutation, which is the most common cause of CF in humans. Login to comment 101 ABCC7 p.Trp1282* monly caused by a mutation that creates a termination codon at residue 1282 in the CFTR coding sequence (W1282X). Login to comment 102 ABCC7 p.Trp1282* ABCC7 p.Ser489* Similar to the S489X mutation in our CFTR(-1-) mice, the W1282X mutation is expected to result in a truncated CFTR protein. Login to comment 163 ABCC7 p.Ser489* However, the phenotype associated with the S489X mutation also differs in obvious ways from the symptoms commonly associated with human CF. Login to comment 172 ABCC7 p.Ser489* With respect to genetic influences, it is possible that since the S489X mutation is still on a heterogeneous genetic background, and since only a small percentage of CFTR( -1-) mice survive, we may have selected for genotypes that compensate to some degree for the effects of the S289X mutation. Login to comment