Mouse Models Of Werner Syndrome

There are currently three mouse models of the Werner syndrome: WRN helicase domain deletion mice (WRNAhel/Ahel) (75), WRN truncation mutant mice (presumably null, WRN-/-) (72), and transgenic mice expressing dominant negative WRN (K577M- WRN) (76). These various genetic mutations are depicted schematically in Figure 4.

WRN-deficient mice carry a WRN gene with an in-frame deletion of the he-licase domains III and IV, as described by Lebel and Leder (75). These mice express a mutant WRN, WRNAhel/Ahel, which retains the exonuclease domains and nuclear localization signal. Mouse embryonic stem cells showed hypersensitivity to campthothecin and mitomycin C, and the growth rate of embryonic fibroblasts was progressively reduced as the cells were passaged. The mice exhibited a normal phenotype at least until the age of 12 months (73).

Another mouse line expresses a mutant WRN protein that is truncated in the middle of helicase region, resulting in mice that are functionally null (WRN-/-)


Exonuclease Repeat Helicase

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