| Autor: |
van den Hurk JA; Department of Human Genetics, University Hospital Nijmegen, The Netherlands. j.vandenhurk@antrg.azn.nl, Hendriks W, van de Pol DJ, Oerlemans F, Jaissle G, Rüther K, Kohler K, Hartmann J, Zrenner E, van Bokhoven H, Wieringa B, Ropers HH, Cremers FP |
| Jazyk: |
angličtina |
| Zdroj: |
Human molecular genetics [Hum Mol Genet] 1997 Jun; Vol. 6 (6), pp. 851-8. |
| DOI: |
10.1093/hmg/6.6.851 |
| Abstrakt: |
Choroideremia (CHM) is an X-linked progressive eye disorder which results from defects in the human Rab escort protein-1 (REP-1) gene. A gene targeting approach was used to disrupt the mouse chm/rep-1 gene. Chimeric males transmitted the mutated gene to their carrier daughters but, surprisingly, these heterozygous females had neither affected male nor carrier female offspring. The targeted rep-1 allele was detectable, however, in male as well as female blastocyst stage embryos isolated from a heterozygous mother. Thus, disruption of the rep-1 gene gives rise to lethality in male embryos; in female embryos it is only lethal if the mutation is of maternal origin. This observation can be explained by preferential inactivation of the paternal X chromosome in murine extraembryonic membranes suggesting that expression of the rep-1 gene is essential in these tissues. In both heterozygous females and chimeras the rep-1 mutation causes photoreceptor cell degeneration. Consequently, conditional rescue of the embryonic lethal phenotype of the rep-1 mutation may provide a faithful mouse model for choroideremia. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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