Disease relevance of Hoxb8

• Plasmids were constructed containing Xenopus laevis Hox-2.5 and -2.4 coding sequences linked to a human cytomegalovirus promoter (CMV-Hox-2.5 and CMV-Hox-2.4) [1].
• The presence of an altered Hox-2.4 gene in the WEHI3B murine myeloid leukemia suggests that homeobox genes may contribute to neoplasia [2].
• Bone marrow cells were infected with Hox-2.4 retrovirus and then either cultured in agar or transplanted into irradiated mice [3].
• NIH 3T3 fibroblast clones bearing the activated Hox-2.4 gene produced fibrosarcomas in nude mice [4].
• In contrast, this first ganglion did persist in the Hoxb-8 gain-of-function transgenic mice [5].

Psychiatry related information on Hoxb8

• The aberrant behavior observed in Hoxb8 mutants is not unlike that of humans suffering from the OC-spectrum disorder, trichotillomania [6].

High impact information on Hoxb8

• Transgenic embryos were generated carrying a Hoxb-8 transgene under control of the mouse RAR beta 2 promoter, which extends the normal expression domain to more anterior regions of the embryo [7].
• Ectopic expression of Hoxb-8 causes duplication of the ZPA in the forelimb and homeotic transformation of axial structures [7].
• We report that mice with disruptions of Hoxb8 show, with 100% penetrance, excessive grooming leading to hair removal and lesions [6].
• In this issue of Neuron, Greer and Capecchi (2002) report that Hoxb8 mutant mice exhibit this behavioral phenotype [8].
• These Hoxb8 mutants will be valuable in exploring the genetics and pathophysiology of OC-spectrum disorders as well as strategies for their treatment [8].

Chemical compound and disease context of Hoxb8

• We have started to take advantage of the phenotype of transgenic versus wild-type embryos to understand the mechanisms underlying the ontogeny and degeneration of Froriep's ganglion in wild-type mice, and the role of Hoxb-8 in C1 maintenance in transgenic embryos [5].

Biological context of Hoxb8

• Phenotypes of double and triple mutants reveal that Hoxb8, Hoxc8 and Hoxd8 have redundant functions at upper thoracic and sacral levels, including positioning of the hindlimbs [9].
• Regulation of smooth muscle-specific gene expression by homeodomain proteins, Hoxa10 and Hoxb8 [10].
• Mutational analysis of telokin promoter reporter genes demonstrated that the three homeodomain protein binding sites located between -80 and -75, +2 and +6, and +14 and +17 were required for maximal promoter activation by Hoxa10-1 and maximal inhibition by Hoxb8 [10].
• Using degenerate reverse transcription-PCR coupled to cDNA library screening we identified two homeodomain proteins, Hoxa10 and Hoxb8, which are expressed in adult mouse smooth muscle tissues [10].
• In vivo mutagenesis of the Hoxb8 hexapeptide domain leads to dominant homeotic transformations that mimic the loss-of-function mutations in genes of the Hoxb cluster [11].

Anatomical context of Hoxb8

• The spatio-temporal activity of this element overlaps with rostral extension of the expression domain of endogenous Hoxb5, Hoxb6 and Hoxb8 into the posterior hindbrain [12].
• OBJECTIVE: The homeobox gene Hoxb8 is activated in the murine myelomonocytic cell line WEHI-3B as a result of intracisternal A particle integration [13].
• The results indicate that Hoxb8 is not an indispensable regulator of A-P patterning in the forelimb, unlike suggested by our Hoxb8 gain of function experiments (Charité J, DeGraaff W, Shen S, Deschamps J. Cell 1994;78:589-601) [14].
• Targeted inactivation of Hoxb8 affects survival of a spinal ganglion and causes aberrant limb reflexes [14].
• Hoxb8 has been suggestively implicated in the formation of the zone of polarizing activity (ZPA) in the limb bud [15].

Associations of Hoxb8 with chemical compounds

• Hoxb-8 coding sequences driven by a retinoic acid receptor beta2 promoter fragment were introduced in the mouse germ line by pronuclear injection [5].
• Retinoid signaling is required for the establishment of a ZPA and for the expression of Hoxb-8, a mediator of ZPA formation [16].

Physical interactions of Hoxb8

• Results from gel mobility shift assays demonstrated that Hoxa10-1, Hoxa10-2, and Hoxb8 bind directly to multiple sites in the telokin promoter [10].

Regulatory relationships of Hoxb8

• On the other hand, Hoxb8 inhibited the activity of the telokin, SM22alpha, and smooth muscle alpha-actin promoters [10].
• The homeobox gene Hox-2.4 is transcriptionally activated in cells of the mouse myeloid leukemia WEHI-3B [4].

Other interactions of Hoxb8

• In contrast, cotransfection with CMV-Hox-2.4 eliminated the CAT activity that was driven by the CMV-Hox-2.5 construct [1].
• A survey of 31 leukemia cell lines of the myeloid, lymphoid and erythroid lineages revealed that Hox-2.4 was expressed only in WEHI3B and the pre-B lymphoid line 70Z/3, in which no DNA rearrangement was observed [2].
• We show that a fragment extending 1316 base pairs (bp) upstream of the transcription start site, thus corresponding to the Hox-2.4/Hox-2.3 intergenic sequences is capable of mediating luciferase gene transcription in transfected cells in vitro and lacZ expression in transgenic mice [17].
• To understand the developmental role of Hoxb-8, this relatively 5' Hoxb gene was ectopically expressed in embryonic regions where only more 3' Hox genes are normally expressed [5].
• We have identified a control region in the Hoxb-5/b-4 intergenic region that rostrally extends the Hoxb-8/LacZ expression domain into the posterior hindbrain [18].

Analytical, diagnostic and therapeutic context of Hoxb8

• Finally, we show that ectopic expression of cdx gene products anteriorizes expression of reporter transgenes driven by this regulatory element, as well as that of the endogenous Hoxb8 gene, in a manner that is consistent with them being essential transducers of positional information [19].
• Chromatin immunoprecipitation revealed that the association of PcG proteins, and H3-K9 acetylation and H3-K27 trimethylation around Hoxb8 were distinct in tissues expressing and not expressing the gene [20].

References