Disease relevance of Hoxb6

• The resulting Hox-2.2 misexpression produces early postnatal lethality as well as craniofacial and axial skeletal perturbations that include open eyes at birth, cleft palate, micrognathia, microtia, skull bone deficiencies, and structural and positional alterations in the vertebral column [1].
• In larvae, the Hox-2.2-induced transformations include thoracic denticle belts in place of head structures; in adults, the Hox-2.2 transformations include thoracic legs in place of antennae [2].
• METHODS: Murine hepatoma MH-22A was used for investigation in vitro and in vivo [3].

High impact information on Hoxb6

• We found similar types of regulatory interactions between Hoxb5 and Hoxb6 [4].
• Reminiscent of Hox-2.2, the rostral boundary of zebrafish hox-2.2 expression is located in the posterior region of the hindbrain [5].
• A cDNA clone containing the Hox-2.2 homeobox has been isolated from an adult spinal cord library [6].
• Structure and expression of Hox-2.2, a murine homeobox-containing gene [6].
• Comparisons of the predicted Hox-2.2 protein with other homeodomain-containing proteins revealed four regions of sequence similiarity: an N-terminal octapeptide, a hexapeptide upstream of the homeodomain, the homeodomain, and a glutamic acid-rich region at the C terminus [6].

Biological context of Hoxb6

• Conserved regulatory element involved in the early onset of Hoxb6 gene expression [7].
• The expression patterns of the transgene and Hoxb6 during early stages of mouse development are identical, suggesting that the LPM enhancer is involved in the initial activation of Hoxb6 gene expression in posterior regions of mammalian embryos [7].
• In order to study cis-acting regulatory elements of murine homeobox genes, transgenic mouse embryos were generated which contained the LacZ reporter gene under the control of different fragments from the murine Hoxb6 gene [8].
• Hox-2.2 is nearly identical with its cognate human homeo box Hu-2 [9].
• Homeoboxes Hox-2.2 and Hox-2.3 are the cognates of two previously reported human homeoboxes that belong to a similar gene cluster on a closely related human chromosome (Chr 17), suggesting that homeoboxes may have been preserved as clusters during evolution [10].

Anatomical context of Hoxb6

• A 2 kb limb/LPM (lateral plate mesoderm) enhancer region was identified which reproduced several aspects of the endogenous Hoxb6 gene expression pattern in the mesenchyme of the developing limb buds and the ventro-lateral body region [8].
• Our results are consistent with the idea that in addition to their presumptive role in CNS and vertebrae development, Hox-2.2 gene products are involved in controlling pattern formation in developing limbs [11].
• The transgene driven by the mouse Hoxb-6 promoter was ectopically expressed in the posterior mesenchyme of the forelimb bud, the lateral plate mesoderm, and the whole mesenchyme of the hindlimb bud [12].
• Immunofluorescence analysis of cell lines with differently organized actin cytoskeletons (A431 cells, HeLa cells, mouse hepatoma MH 22A, Zajdela ascitic hepatoma, primary human embryo skin and lung fibroblasts) gave evidence that PLC gamma 1 is colocalized only with cortical actin and not with stress fibers [13].
• Further, the nuclei of highly transformed cell lines (A431 cells, HeLa cells, mouse hepatoma MH 22A, rat Zajdela ascitic hepatoma) were labeled with the anti-PLC gamma 1 antibody [13].

Other interactions of Hoxb6

• These observations suggest that for some aspects of Hoxb-6 gene regulation the integrity of large genomic regions of the Hoxb cluster is required [14].
• Using this assay, we compared transcriptional activation by three chimeric proteins containing the homeodomains of the mouse homeobox genes, Hoxa-5, Hoxb-6, and Hoxc-8 [15].
• RNase protection analysis also revealed two alternatively spliced forms of the Hox 2.2 mRNA are present throughout fetal skin development [16].
• Disruption of the homeobox gene Hoxb-6 in mice results in increased numbers of early erythrocyte progenitors [17].

Analytical, diagnostic and therapeutic context of Hoxb6

• Sequence analysis of the murine Hox-2.2, -2.3, and -2.4 homeo boxes: evolutionary and structural comparisons [9].
• The expression of the Hox 2.2 gene was studied in mouse fetal skin by in situ hybridization with an antisense RNA probe derived from the homeobox region of this gene [16].
• In vivo, the antitumor activity was estimated by monitoring the tumor volume over time, in mice transplanted subcutaneously with MH-22A and treated with Dox and/or PDT [3].

References