Disease relevance of Prrx1

• 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 [1].
• Prostate cancer cells were rendered more sensitive to hydrogen peroxide or an organic hydroperoxide when Prx 1, 2, or 3 but not 4 was partially suppressed, bringing them into the range of sensitivity of mouse cells [2].
• RmpA2, an activator of capsule biosynthesis in Klebsiella pneumoniae CG43, regulates K2 cps gene expression at the transcriptional level [3].

High impact information on Prrx1

• FAK induces expression of Prx1 to promote tenascin-C-dependent fibroblast migration [4].
• However, activated FAK was essential for Prx1 expression [4].
• Pitx2, a paired-related homeobox gene that encodes multiple isoforms, is the gene mutated in the haploinsufficient Rieger Syndrome type 1 that includes dental, ocular and abdominal wall anomalies as cardinal features [5].
• Prx1 and Prx2 are upstream regulators of sonic hedgehog and control cell proliferation during mandibular arch morphogenesis [6].
• The paired-related homeobox gene, prx-1, is expressed in the postmigratory cranial mesenchyme of all facial prominences and is required for the formation of proximal first arch derivatives [7].

Biological context of Prrx1

• 1. This localization, along with the recently described phenotypes of the gene-targeted Prrx1, Prrx2 and double mutant mice, enabled us to search the human disease databases for similar malformations [8].
• Identification of a prx1 limb enhancer [1].
• 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 [1].
• Moreover, transgene expression was diminished in posterior handplate of prx1; prx2 double mutant mice [1].
• Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus [9].

Anatomical context of Prrx1

• 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 [1].
• Mice that lack both Prx1 and Prx2 functions display reduction or absence of skeletal elements in the skull, face, limbs and vertebral column [6].
• This analysis showed that a conserved domain (PRX), found in both Prx1 and Prx2, activated transcription in NIH 3T3 cells [10].
• However, the Prx1-/- and Prx1/Prx2 double-null mutants showed a vascular abnormality with an abnormal positioning and awkward curvature of the aortic arch in addition to a misdirected and elongated ductus arteriosus, and in two of seven combined mutants, an anomalous retro-oesophageal right subclavian artery [9].
• Initial studies revealed that Prx1 localizes to differentiating endothelial cells (ECs) within the fetal lung mesenchyme, and later within ECs forming vascular networks [11].

Associations of Prrx1 with chemical compounds

• Evidence is provided that this increase of fibrin binding is mediated by the kringle 2 (K2) domain that contains a lysine-binding site [12].
• The k1 value for tcwt-rtPA was not influenced by the presence of epsilon-aminocaproic acid, suggesting that the lysine-binding site associated with the kringle 2 (K2) region of tPA does not modulate the rate of its initial interaction with rPAI-1 [13].
• This localization strongly suggests that CLC-K2 confers the basolateral conductance in the type A intercalated cells where Cl(-) is taken up by the anion exchanger in exchange for HCO(3)(-) at the basolateral membranes [14].
• CLC-K2, a kidney-specific member of the CLC chloride channel family, is thought to play an important role in the transepithelial Cl(-) transport in the kidney [14].
• These results suggest that a novel set of zinc finger proteins may help regulate the strict tissue and nephron segment-specific expression of CLC-K1 and CLC-K2 channel genes through their GA cis element [15].

Other interactions of Prrx1

• Furthermore, antibody-blocking studies showed that TN-C is required for Prx1-dependent vascular network formation on Matrigel [11].
• Prx1-/- and Prx double-gene-targeted mice revealed similar spectra of vascular anomalies, but double mutants appeared to be more seriously affected [9].
• The Pmx gene is located on Chromosome 1, approximately 3.3 cM distal to the Gsh-4 homeobox locus [16].
• We identified a homeobox-containing gene, Prx-1, isolated from the chick limb bud cDNA library [17].

Analytical, diagnostic and therapeutic context of Prrx1

• Immunocytochemistry/histochemistry showed that a TN-C-rich ECM surrounds Prx1-positive pulmonary vascular networks both in vivo and in tissue culture [11].
• Sequence analysis reveals that the homeobox of K-2 is 77.6% homologous at the nucleotide level and 97% identical at the amino acid sequence level to another murine gene, S8 [18].
• We have identified a novel homeobox gene, designated K-2, using a reverse transcription PCR cloning strategy [18].
• Using an in situ hybridization method, the Prx-1 gene is shown to be expressed predominantly in the limb bud and visceral arches [17].
• The sequence of the Pmx transcript has been extended toward the 5' end and corresponds in size to one of the transcripts previously detected by Northern blot analysis [16].

References