| First Author | Yan W | Year | 1998 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 39 |
| Issue | 13 | Pages | 2529-36 |
| PubMed ID | 9856762 | Mgi Jnum | J:51361 |
| Mgi Id | MGI:1315141 | Citation | Yan W, et al. (1998) Selective degradation of nonsense beta-phosphodiesterase mRNA in the heterozygous rd mouse. Invest Ophthalmol Vis Sci 39(13):2529-36 |
| abstractText | PURPOSE. TO investigate the molecular mechanism relating phenotype and genotype in the rd mouse, mRNA and pre-mRNA levels derived from the wild-type and position-347 nonsense mutant beta-phosphodiesterase (beta-PDE) genes were determined and compared with the corresponding gene copy ratios. METHODS. Total RNA and genomic DNA was isolated from the retinas of three heterozygous rd/+ mouse strains. For each, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the ratio of wild- type and rd beta-phosphodiesterase pre-mRNA and mature mRNA. The gene copy ratio between wild-type and rd beta- PDE was also determined by quantitative PCR. RESULTS. The pre-mRNA ratio of wild-type versus nonsense mutant was close to 1:I, whereas the corresponding mRNA ratio was greater than 3.1, even though the gene copy ratio was confirmed to be 1:1. CONCLUSIONS. The equivalence of pre-mRNA ratio level for wild-type and nonsense mutant in the rd/+ retina indicates that both genes were transcribed at similar levels. Thus, neither the nonsense mutation at position 347 nor the intron 1 retroviral insertion also present in the rd gene seem to have affected gene transcription. In contrast, the strain-independent bias favoring wild-type mature mRNA in vivo suggests a specific degradation of mutant transcript during or after pre-mRNA splicing. This allele-specific degradation set-yes to decrease mutant transcript levels dramatically in all rd strains, and suggests that photoreceptor cells have the capacity to reduce the level of an mRNA containing a nonsense mutation. |
