ABCC7 p.Thr94Ile
| Predicted by SNAP2: | A: N (57%), C: N (57%), D: D (66%), E: D (71%), F: D (66%), G: D (59%), H: D (63%), I: D (53%), K: D (75%), L: D (53%), M: D (59%), N: N (53%), P: D (66%), Q: D (63%), R: D (75%), S: N (82%), V: N (53%), W: D (85%), Y: D (71%), |
| Predicted by PROVEAN: | A: N, C: N, D: D, E: D, F: N, G: D, H: D, I: N, K: N, L: N, M: N, N: N, P: D, Q: N, R: N, S: N, V: N, W: D, Y: N, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Skipping of exon 9 of human CFTR in YAC-transgenic... Genomics. 2001 Oct;77(3):127-34. Manson A, Huxley C
Skipping of exon 9 of human CFTR in YAC-transgenic mice.
Genomics. 2001 Oct;77(3):127-34., [PMID:11597137]
Abstract [show]
Exon 9 of the human gene CFTR is skipped in some mRNA transcripts in human tissues. The level of skipping correlates with the number of TG's and T's in the 5' splice acceptor of exon 9. Poorly spliced alleles are associated with mild cystic fibrosis related phenotypes. Here we describe transgenic mice carrying a yeast artificial chromosome (YAC) with the intact human gene CFTR. When the YAC carries 10 TG's and 7 T's at the splice acceptor, there is about 50% skipping of exon 9 in most tissues, whereas 12 TG's and 5 T's give about 90% skipping. The level of skipping is quite uniform over many tissues, except the testis, in which there is a much higher level of correct splicing. These mice confirm that the TG(m)T(n) polymorphism has an effect on splicing and should be valuable for studying this phenomenon.
Comments [show]
None has been submitted yet.
No. Sentence Comment
71 This is a missense mutation replacing threonine 94 with isoleucine (T94I) and should have no effect on the splicing of exon 9.
X
ABCC7 p.Thr94Ile 11597137:71:38
status: NEWX
ABCC7 p.Thr94Ile 11597137:71:68
status: NEW72 We generated one line of mice, A10, with the YAC carrying the TG12T5 splice site and the R117T and T94I mutations.
X
ABCC7 p.Thr94Ile 11597137:72:99
status: NEW73 Another, 7T44, was generated with a YAC carrying the original TG10T7 splice site with the R117H and T94I mutations.
X
ABCC7 p.Thr94Ile 11597137:73:100
status: NEW79 However, we cannot determine whether this is due to the T94I mutation, the R117H mutation, and/or low splicing efficiency.
X
ABCC7 p.Thr94Ile 11597137:79:56
status: NEW80 As further controls, two cell lines (F7T.2 and F7T.5) were made with the YAC carrying the R117H and T94I mutations and the 7T splice site.
X
ABCC7 p.Thr94Ile 11597137:80:100
status: NEW94 mRNA (n)a of transgeneb TgN(yCFTR)T30Clh T30 TG10T7 2 0.108 (2) 11% TgN(yCFTR)T57Clh T57 TG10T7 1 0.109 (2) 22% TgN(yCFTR)A10Clh A10 TG12T5, R117H, T94I 6 0.205 (2) 7% TgN(yCFTR)7T44Clh 7T44 TG10T7, R117H, T94I nd nd nd Cell line name F7T.2 TG10T7, R117H, T94I 2 0.178 (2) 18% F7T.5 TG10T7, R117H, T94I 8 0.825 (3) 21% a Number of independent cDNA and RT-PCR reactions.
X
ABCC7 p.Thr94Ile 11597137:94:148
status: NEWX
ABCC7 p.Thr94Ile 11597137:94:206
status: NEWX
ABCC7 p.Thr94Ile 11597137:94:256
status: NEWX
ABCC7 p.Thr94Ile 11597137:94:298
status: NEW125 The level of skipping of exon 9 in the lung, trachea, gall bladder, duodenum, colon, uterus, and epididymis of A10 mice (5Ts, R117H, and T94I) was quite uniform at about 91%.
X
ABCC7 p.Thr94Ile 11597137:125:137
status: NEW127 A10 differs from T30 not only at the splice site of exon 9, but also in having the R117H and T94I mutations in exon 4.
X
ABCC7 p.Thr94Ile 11597137:127:93
status: NEW128 To determine whether the R117H and T94I mutations were affecting splicing of exon 9, we also determined the level of skipping of exon 9 in the duodenum and testis of a 7T44 mouse.
X
ABCC7 p.Thr94Ile 11597137:128:35
status: NEW130 Although slightly higher than the values obtained for T30 mice, the R117H and T94I mutations do not account for the much higher levels of skipping in the A10 line than the T30 line.
X
ABCC7 p.Thr94Ile 11597137:130:78
status: NEW139 Our original intention was to also study the R117H missense mutation that was introduced into exon 4, but another missense mutation, T94I, was inadvertently introduced into exon 4 at the same time so the effect of the R117H mutation could not be studied.
X
ABCC7 p.Thr94Ile 11597137:139:133
status: NEW141 In this case, the presence of the R117H and T94I mutations in exon 4 has little effect on the level of skipping of exon 9 as indicated by the similar splicing in the lines T30 and 7T44, which differ only by the two mutations in exon 4 (Fig. 5).
X
ABCC7 p.Thr94Ile 11597137:141:44
status: NEW213 This point mutation causes a missense mutation, T94I, in the coded protein.
X
ABCC7 p.Thr94Ile 11597137:213:48
status: NEW