TBX5 and Holt-Oram syndrome: This hypomorphic misexpression of the transgene only partially rescues forelimb bud initiation defects caused by the conditional deletion of Tbx5 (Tbx5lox/lox;Prx1Cre;Prx1-Tbx) and recapitulates many features of the upper limb defects seen in HOS patients, for example an anterior bias to the structures affected (including triphalangeal thumb, absent thumb), defects in the scapula and in more severe examples, phocomelia (Fig 1A–1C).