International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

WEDNESDAY OCTOBER 20

8.45pm – 9.00pm

STUDYING THE ROLE OF THE KINESIN-LIKE MOTOR PROTEIN, EG5, IN TUMORIGENESIS, GENOME INSTABILITY, AND AGING.

Castillo A, Justice MJ

Baylor College of Medicine, Houston, United States

Formation and stabilization of the mitotic spindle is dependent on the kinesin-like motor protein Eg5.  Chemical and antibody inhibition have shown that disruption of Eg5 function leads to mitotic arrest, monopolar spindles, and aneuploidy.  In cultured post-mitotic axons, inhibition can disturb axonal outgrowth. Additionally, Eg5 has been shown to be regulated by the centrosomal kinase, Aurora-A/STK15, which is often over expressed in numerous cancers. We showed that Eg5 is up regulated in B-cell leukemias from AKXD recombinant inbred mice with proviral insertions at lymphoid viral insertion site (Lvis1).  Transgenic mice overexpressing Eg5 in lymphoid tissues were generated and aged to determine if misexpression of Eg5 can lead to tumor development.  Aged mice develop multiple tumor types, but also display distended bladders, dermatitis, and chronic piloerection.  Based on Eg5’s involvement in cell cycle mechanics and post-mitotic neurons, our observations suggest a premature aging syndrome with potential skin and neurogenic bladder problems.  In parallel, Eg5 loss of function mice were generated from genetrapped ES cells and display early embryonic lethality. Conditional targeting of Eg5 will circumvent this lethality and be used to study neuronal and tissue specific functions.

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