Use of null mutant (knockout) mice to define the pathways that transgenes use to generate disease-relevant phenotypes. In these experiments, transgenic mice with a disease-relevant phenotype (for example, fibrosis or inflammation) are mated with mice that have a null mutation of a downstream gene that is believed to play an important role in the generation of this phenotype. Transgene-positive (TG[+]) and transgene-negative (TG[–]) mice are generated that have normal downstream genes (+/+), are heterozygote knockout at the downstream gene in question (+/–), or are null-mutant for the downstream gene in question (–/–). The presence and intensity of the phenotypes of these mice are then compared. These comparisons allow an investigator to define the role(s) that this downstream gene plays in the generation of the pathologic response.