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Gene Review

MEOX2  -  mesenchyme homeobox 2

Homo sapiens

Synonyms: GAX, Growth arrest-specific homeobox, Homeobox protein MOX-2, MOX2, Mesenchyme homeobox 2
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Disease relevance of MEOX2

  • PURPOSE: We evaluated the long-term efficacy of subureteral glutaraldehyde cross-linked collagen injection (GAX 35) for endoscopic treatment of vesicoureteral reflux in patients with neurogenic bladder dysfunction due to meningomyelocele [1].
  • GAX collagen in the treatment of urinary incontinence in elderly women: a two year follow up [2].
  • Studies of both acute and chronic pulmonary toxicity reveal that when GAX is embolized directly into the pulmonary circulation it causes adverse effects only by mechanical blockage of pulmonary arteries [3].
  • Subject to a negative skin test for allergy, each patient underwent the implantation of GAX collagen (Contigen), a biocompatible product causing no foreign body reaction [4].
  • Avoidance of useless overcorrection, better resistance to collagenase, and less induced hypersensitivity differentiate GAX from ZCI [5].

High impact information on MEOX2

  • The link of MEOX2 to neurovascular dysfunction in Alzheimer disease provides new mechanistic and therapeutic insights into this illness [6].
  • We conclude that GAX activates p21(WAF1/CIP1) through multiple upstream AT-rich sequences [7].
  • There was an absolute requirement for the homeodomain, whereas deleting the C-terminal domain decreased but did not abolish transactivation of the p21(WAF1/CIP1) promoter by GAX [7].
  • GAX was able to bind to A6 in a homeodomain-dependent manner and thereby activate the expression of a reporter gene coupled to this sequence, and this activation was abolished by mutating specific residues in this sequence [7].
  • Mox1 and Mox2 homeobox genes have been shown to be critical in axial skeleton and in limb muscle development respectively [8].

Biological context of MEOX2


Anatomical context of MEOX2

  • The molecular mechanisms by which Mesenchyme Homeobox 2 (Meox2) regulates the proliferation, differentiation and migration of vascular smooth muscle cells and cardiomyocytes are not known [9].
  • Now, a new study by Zlokovic and colleagues reveals that the vascular gene MEOX2 has a low expression in cultured brain endothelial cells from AD patients [10].
  • The GAX homeobox gene is expressed in the cardiovascular tissues of the adult rat, including heart, lung, kidney, and blood vessels [12].
  • In term placenta, MSX2 and MOX2 are expressed in the syncytiotrophoblast [13].
  • Of the 16 ureters treated with GAX 65 14 (87.5%) were reflux-free at the 3-month followup [14].

Associations of MEOX2 with chemical compounds

  • The minimal RNF10 binding region of MEOX2 was determined to be a central region between the histidine/glutamine rich domain and the homeodomain (amino acids 101-185) [9].
  • The aim of the study was to evaluate the efficacy of anal glutaraldehyde cross-linked (GAX) collagen injections in patients with a surgically incorrectable disorder [15].
  • More recently, two major materials have been developed that seem to be useful in treating stress incontinence by periurethral injection: Polytef paste and GAX collagen [16].

Physical interactions of MEOX2


Regulatory relationships of MEOX2

  • Our results also demonstrated that MEOX2 activation of the p21WAF1 promoter was enhanced by RNF10 co-expression [9].

Other interactions of MEOX2

  • The amino terminal region of RNF10, containing the RING finger domain, was not essential for the binding to MEOX2 [9].

Analytical, diagnostic and therapeutic context of MEOX2

  • The human GAX locus was mapped by fluorescence in situ hybridization to the short arm of chromosome 7 at band p21 [12].
  • Molecular cloning and localization of the human GAX gene to 7p21 [12].
  • The human GAX cDNA was obtained by an anchored-PCR approach using cDNA templates from cardiovascular tissues and amplification primers designed from sequence information of the rat GAX cDNA and the homeodomain-containing exon of the human GAX gene [12].
  • Next, we performed chromatin immunoprecipitation and found, approximately 15 kb upstream of the p21(WAF1/CIP1) ATG codon, an ATTA-containing GAX-binding site (designated A6) with a sequence similar to that of other homeodomain-binding sites [7].
  • All had anorectal physiology and endoanal ultrasonography before and after GAX collagen injections [15].


  1. Long-term efficacy of subureteral collagen injection for endoscopic treatment of vesicoureteral reflux in neurogenic bladder cases. Haferkamp, A., Möhring, K., Staehler, G., Gerner, H.J., Dörsam, J. J. Urol. (2000) [Pubmed]
  2. GAX collagen in the treatment of urinary incontinence in elderly women: a two year follow up. Khullar, V., Cardozo, L.D., Abbott, D., Anders, K. British journal of obstetrics and gynaecology. (1997) [Pubmed]
  3. Glutaraldehyde cross-linked collagen (GAX): a new material for therapeutic embolization. Strother, C.M., Laravuso, R., Rappe, A., Su, S.L., Northern, K. AJNR. American journal of neuroradiology. (1987) [Pubmed]
  4. Injectable collagen for type 3 female stress incontinence: the first 50 Australian patients. Stricker, P., Haylen, B. Med. J. Aust. (1993) [Pubmed]
  5. Correction of glottic insufficiency by collagen injection. Remacle, M., Marbaix, E., Hamoir, M., Bertrand, B., van den Eeckhaut, J. The Annals of otology, rhinology, and laryngology. (1990) [Pubmed]
  6. Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease. Wu, Z., Guo, H., Chow, N., Sallstrom, J., Bell, R.D., Deane, R., Brooks, A.I., Kanagala, S., Rubio, A., Sagare, A., Liu, D., Li, F., Armstrong, D., Gasiewicz, T., Zidovetzki, R., Song, X., Hofman, F., Zlokovic, B.V. Nat. Med. (2005) [Pubmed]
  7. The Homeobox Gene GAX Activates p21WAF1/CIP1 Expression in Vascular Endothelial Cells through Direct Interaction with Upstream AT-rich Sequences. Chen, Y., Leal, A.D., Patel, S., Gorski, D.H. J. Biol. Chem. (2007) [Pubmed]
  8. Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors. Stamataki, D., Kastrinaki, M., Mankoo, B.S., Pachnis, V., Karagogeos, D. FEBS Lett. (2001) [Pubmed]
  9. Characterization of Mesenchyme Homeobox 2 (MEOX2) transcription factor binding to RING finger protein 10. Lin, J., Friesen, M.T., Bocangel, P., Cheung, D., Rawszer, K., Wigle, J.T. Mol. Cell. Biochem. (2005) [Pubmed]
  10. Cerebrovascular gene linked to Alzheimer's disease pathology. de la Torre, J.C. Trends in molecular medicine. (2005) [Pubmed]
  11. Isolation of the human MOX2 homeobox gene and localization to chromosome 7p22.1-p21.3. Grigoriou, M., Kastrinaki, M.C., Modi, W.S., Theodorakis, K., Mankoo, B., Pachnis, V., Karagogeos, D. Genomics (1995) [Pubmed]
  12. Molecular cloning and localization of the human GAX gene to 7p21. LePage, D.F., Altomare, D.A., Testa, J.R., Walsh, K. Genomics (1994) [Pubmed]
  13. The homeobox genes MSX2 and MOX2 are candidates for regulating epithelial-mesenchymal cell interactions in the human placenta. Quinn, L.M., Latham, S.E., Kalionis, B. Placenta (2000) [Pubmed]
  14. GAX 65: new injectable cross-linked collagen for the endoscopic treatment of vesicoureteral reflux--a double-blind study evaluating its efficiency in children. Frey, P., Gudinchet, F., Jenny, P. J. Urol. (1997) [Pubmed]
  15. Glutaraldehyde cross-linked collagen in the treatment of faecal incontinence. Kumar, D., Benson, M.J., Bland, J.E. The British journal of surgery. (1998) [Pubmed]
  16. Periurethral injection for the treatment of urinary incontinence. Benshushan, A., Brzezinski, A., Shoshani, O., Rojansky, N. Obstetrical & gynecological survey. (1998) [Pubmed]
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