Abstract: 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.