Disease relevance of Rax

• Cre-mediated conversion of Rx(flox) generates the RxDelta2 allele, which, when homozygous, results in an Rx-null phenotype that includes perinatal lethality, anophthalmia, and anterior neural and craniofacial defects [1].

High impact information on Rax

• Consistent with the loss-of-function results, the injection of Xvax1 results in a down-regulation of Rx [2].
• The predicted amino acid sequence of Rax comprises a protein with a paired-type homeobox, as well as the octapeptide that is found in many paired-type homeobox genes [3].
• Specification of the retinal fate of mouse embryonic stem cells by ectopic expression of Rx/rax, a homeobox gene [4].
• Based on findings that mutations in the Rx/Rax homeobox genes in mice and fish lead to defects in retinal development and result in animal models of anophthalmia, we screened 75 individuals with anophthalmia and/or microphthalmia for mutations in the human RAX gene [5].
• EnRaxLDeltaC, but not the dominant negative Rax (EnRaxDeltaC), caused a significant reduction in expression of early markers of photoreceptor cells [6].

Biological context of Rax

• In contrast, in homozygous Small eye embryos that lack Pax6 function, Rx shows normal activation in the anterior neural plate and normal upregulation in the optic vesicle/retinal progenitor cells [7].
• Rx-null homozygotes lack optic pits, which are the earliest ocular structures [1].
• The 5' upstream regulatory sequences of the medaka fish Rx gene are functionally conserved during evolution to a degree that they direct gene expression into the Rx-expressing field of cells in mice [8].
• Since resiniferatoxin is a poor activator of PKC, it is probable that the Ca2(+)-independent Rx-kinase plays a role in activation of the macrophage respiratory burst following stimulation by zymosan [9].
• Investigation of the tissue distribution of the calcium independent kinase, Rx kinase; which is distinct from known isozymes of protein kinase C [10].

Anatomical context of Rax

• Function of Rx, but not Pax6, is essential for the formation of retinal progenitor cells in mice [7].
• The Rx homeobox gene is a transcriptional regulator indispensable for development of the eye and ventral forebrain [1].
• Survey for paired-like homeodomain gene expression in the hypothalamus: restricted expression patterns of Rx, Alx4 and goosecoid [11].
• Rx was additionally found in the posterior pituitary and in cells aligning the bottom of the third ventricle [11].
• Furthermore, we found expression of Rx in the pineal gland, along with Alx4 [11].

References