Smad9^tm1Mwst

A targeting construct was designed to flank exon 3 with loxP sites and insert a PGK-neo into intron 3 with a 3' loxP site. RT-PCR demonstrated a hybrid transcript in mutant mice, utilizing a splice site 5 bp upstream of the initiationg ATG. This aberrant splicing caused neo to be out of frame with the endogenous transcript, resulting in a premature stop codon, and thereby allowing synthesis of a truncated Smad9 protein lacking about three-fourths of the MH2 domain. Real time ePCR demonstrated that transcript is reduced in the adult mutant brain, and that this allele is a hypomorph. (J:99098)