Producing transgenic mammal comprising reduced expression of DNAse I, useful for studying development of systemic lupus erythematosus and in drug screening

摘要

Producing, (P), a transgenic, non-human mammal (A) that has at least partial reduction in activity of DNAse I (I), is new. Production of a transgenic, non-human mammal (A) that has at least partial reduction in activity of DNAse I (I), where an embryonal stem cell is transfected with a (I)-targeting vector and stable clones isolated in which the endogenous (I)-encoding gene has been (partially) replaced by other sequences or destroyed, as a result of homologous recombination with parts of the targeting vector. These clones are implanted into a suitably prepared surrogate dam and progeny selected for presence of DNA incorporation. Independent claims are also included for the following: (1) (A) produced by P; (2) recombinant (I)-targeting vector used for homologous recombination; (3) stably transfected cells in which all or part of the (I)-encoding gene has been replaced by another DNA sequence; (4) model system for analysis of either the origins of SLE (systemic lupus erythematosus) or treatments of diseases, specifically SLE, that includes at least one (A); (5) testing new pharmaceuticals for activity against SLE, using (A) or stable cell clones or organs derived from (A); and (6) testing the affects of genetic, biological, chemical and physical factors on development of SLE.