ABCMdb

PMID: 16740913

Jin R, Hodges CA, Drumm ML, Palmert MR
The cystic fibrosis transmembrane conductance regulator (Cftr) modulates the timing of puberty in mice.
J Med Genet. 2006 Jun;43(6):e29., [PubMed]

Sentences

No. Mutations Sentence Comment

131 ABCC7 p.Ser489* Methods: To examine this hypothesis, we investigated pubertal timing (as assessed by vaginal opening (VO)) in a mouse model of CF (Cftrtm1Unc ) engineered to produce a truncated Cftr mRNA and referred to as S489X. Login to comment 146 ABCC7 p.Ser489* First, B6 mice heterozygous for the S489X mutation that generates a stop codon in the coding sequence of exon 10 of Cftr (B6.129P2-Cftrtm1Unc /J),20 were purchased from Jackson Laboratory (Bar Harbor, ME; stock no. Login to comment 148 ABCC7 p.Ser489* ABCC7 p.Ser489* This mutation leads to a truncated protein product similar to many human CF mutations.20 Heterozygous S489X mice (referred to as S489X2 /S489X+ ) were bred and the progeny homozygote, heterozygote, or negative (wild type, WT) for the S489X mutation were studied. Login to comment 153 ABCC7 p.Ser489* In the colony described here, the DF508 and S489X lines are backcrossed to B6 mice every five generations to ensure genetic fidelity and prevent genetic drift. Login to comment 154 ABCC7 p.Ser489* Live animals were genotyped at 7 days after date of birth by PCR analysis of DNA extracted from a toe removed for mouse identification.24 WT mice from the S489X or DF508 matings are both predicted to be indistinguishable from B6 mice due to the backcrossing of these alleles. Login to comment 155 ABCC7 p.Ser489* Because there were no observable phenotypic differences between the WT mice generated from the two mating strategies (mean timing of vaginal opening (VO) 31.3¡1.4 days for S489X WT (n = 14) and 31.3¡1.5 days for DF508 WT (n = 12)), WT animals were assessed as a single group. Login to comment 157 ABCC7 p.Ser489* For the S489X mice, the p values for comparison of homozygote and heterozygote mice to WT mice were ,0.00001 and 0.00004, respectively; for the DF508 mice, the p values for comparison of homozygote and heterozygote mice to WT mice were 0.00007 and 0.0002, respectively. Login to comment 172 ABCC7 p.Ser489* ABCC7 p.Ser489* ABCC7 p.Ser489* ABCC7 p.Ser489* S489X- /S489X+ 100 90 70 80 60 40 50 30 20 0 10 80 Age (days) S489X- /S489X - MicewithVO(%) 20 7570656055504540353025 WT Figure 1 Comparison of the timing of vaginal opening (VO) for S489X mice. Login to comment 180 ABCC7 p.Ser489* RESULTS VO occurred significantly later in S489X homozygous knockout (S489X2 /S489X2 ) mice than in WT B6 mice (table 1, fig 1). Login to comment 181 ABCC7 p.Ser489* The S489X CF mice also grew more slowly than WT mice and had not even reached a mean weight of 15 g by 50 days of age; thus, despite the delay in VO, the S489X2 / S489X2 mice experienced VO at significantly lower mean body weights than the WT animals. Login to comment 182 ABCC7 p.Ser489* To investigate the direct effects of Cftr on pubertal timing without the confounding effects of chronic disease, mice heterozygous for the S489X mutation were examined. Login to comment