The University of British Columbia

Frank R Jirik

Christopher J Ong

Lorne A Clarke

John J Priatel

Methods and DNA constructs are provided for detection and manipulation of a target eukaryotic gene whose expression is restricted to certain tissues or specialized cell types. The methods include transforming a cell with a first indicator component under the control of a promoter selected for its restricted expression in a particular cell or tissue. The cell is also transformed with a gene trap vector encoding a second indicator component. The cell is allowed to differentiate to produce specialized cell or tissue which is monitored for expression of both the first and second indicator components, thereby detecting a gene into which the trap vector has integrated which is expressed in the same cell or tissue type as the selected promoter.

Complementation trap

A mouse which is homozygous for a disruption in the IDUA gene, but which has normal expression for the SAT-1 gene can be used for evaluating therapeutic agents for use in treating mucopolysaccharidosis Type I, by administering the therapeutic agent to the mouse, and evaluating the mouse for tissue pathology associated with iduronidase deficiency. The mouse can also be used for evaluating the ability of a targeting system to deliver a therapeutic agent to selected tissues or organs by administering an effective iduronidase replacement therapy coupled to the targeting system to a mouse which is homozygous for a disruption in the IDUA gene, but which has normal expression for the SAT-1 gene; and evaluating at least the selected tissue or organ from the mouse for pathology associated with iduronidase deficiency. Targeting systems which can be evaluated using this methodology include targeting moieties which selectively bind to or associate with selected cell types and in vivo and ex vivo gene therapy systems.

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Vancouver, Canada

Frank R Jirik