Identification of a prx1 limb enhancer

Mice with a loss of function of prx1, a paired-related homeobox gene formerly called Mhox, showed craniofacial defects, limb shortening, and incompletely penetrant spina bifida. To investigate the mechanisms that regulate prx1 expression, we analyzed a 2.4-kb prx1 genomic flanking region in transgenic mice. This region of the prx1 gene contains an enhancer element that directs expression of a LacZ reporter gene in limb bud mesenchyme and a subset of craniofacial mesenchyme. Deletional analysis in transgenic founders identified a necessary 530-bp core element. Comparison of this core element with human Prx1 sequence showed two highly conserved cassettes that also contained a prx recognition element. Moreover, transgene expression was diminished in posterior handplate of prx1; prx2 double mutant mice. Our data reveal that the prx1 limb enhancer is proximally located within the prx1 gene and suggest that prx1 may have an autoregulatory function in limb mesenchyme.