Abstract: Disclosed is a genetically modified non-human animal that is a model for defective folate transport. Specifically the non-human animal comprises a genetic modification that results in decreased or absent expression and/or biological activity of the endogenous reduced folate carrier. The animal can be further modified by introduction into the genome of a nucleic acid molecule encoding the human reduced folate carrier. Such an animal can be used in methods to identify compounds useful for treating a variety of conditions associated with defective folate transport, or for the identification of anti-folate compounds useful for treating cancer. The animal can also be used to study the biochemical and molecular events associated with folate transport. Compounds identified using such a model are valuable for therapeutic treatments.