Abstract:
: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.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
van den Hurk JA,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 FPdoi
10.1093/hmg/6.6.851subject
Has Abstractpub_date
1997-06-01 00:00:00pages
851-8issue
6eissn
0964-6906issn
1460-2083pii
dda121journal_volume
6pub_type
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