Gene expression in a mouse model of Pantothenate Kinase-Associated Neurodegeneration

A mouse model lacking systemic expression of Pank1 together with neuronal deletion of Pank2 was generated and revealed a developmental requirement for CoA that, when deficient, resulted in abnormal motor behavior preceding early death. Neuronal Pank2 expression in Pank1-/-Syn-Pank2-/- double knockout mice (dKO) decreased starting at P9-11 and brain CoA levels did not increase subsequently, in contrast to wild-type matched control animals. The Pank1-/-Syn-Pank2-/- dKO mice developed a forelimb deformity and abnormal gait behavior, similar to PKAN patients, and lost weight when brain CoA became depressed relative to wild-type levels. Comparative gene expression analysis revealed significant alteration of a relatively small selection of genes, including reduction of gene transcripts affecting heme and hemoglobin synthesis together with upregulation of gene transcripts related to the response to oxygen/glucose deprivation. Overall design: Compare gene expression of knockout mice vs control at days 10 and 20, segregated for sex.