Abstract: The present invention provides a genetically-modified non-human animal whose somatic and germ cells contain a gene encoding an altered form of an DHX36 gene, the altered DHX36 haviang been targeted to replace a wild-type DHX36 gene into the animal or an ancestor of the animal at an embyonic stage using embryonic stem cells. An ideal use of the genetically-modified non-human animal of the invention is the use as an experimental model for muscular dystrophy, e.g. spinal muscular atrophy, to identify e.g. new treatments for muscular dystrophy and or study its pathogenesis.

Abstract: The present invention relates to a method for treating cancer in a subject by inhibiting DHX36, by administering to said subject a therapeutically effective amount of a modulator of DHX36.

Abstract: A method is provided for isoform specific gene expression in a mammalian cell in the absence of other isoforms. The method uses RNAi to achieve the specific expression.

Abstract: Methods for screening agents effective against diabetes or preventing the onset of diabetes, in particular Type 2 diabetes, are provided. In one aspect of the invention, the method encompasses assaying for PAI-1 activity in the presence of a candidate agent; and correlating a decrease in PAI-1 activity relative to when the candidate agent is absent with the presence of a potential agent effective against diabetes. Alternatively, E2F activity is detected, an increase in E2F activity reflecting a decrease in PAI-1 activity. Also provided are methods for inhibiting PAI-1 activity, pharmaceutical agents and compositions.