Pitx1 Haploinsufficiency Causes Clubfoot in Humans and Mice

To identify genes regulated by Pitx1 during early hindlimb development, we compared gene expression differences between hindlimb buds from E12.5 Pitx1+/+ and Pitx1-/- mice on the Illumina MouseRef-8 expression Bead Chip. Genes involved in muscle development GeneGO processes were highly enriched in our dataset, specifically in down-regulated genes. This data is consistent with the reduced muscle volumes that were observed in the clubfoot limbs of our adult mice. Hindlimb buds were collected from Pitx1+/- mated mice at embryonic day E12.5 and genotypes were determined by PCR of DNA isolated from tails.