Disease relevance of Hoxb7

• The developmental malformations that resulted when the chicken beta-actin promoter was used to direct widespread expression of the Hox-2.3 gene in transgenic mice included early postnatal death as well as craniofacial abnormalities, including open eyes and cleft palate [1].
• DNA-binding activity of the murine homeodomain protein Hox-2.3 produced by a hybrid phage T7/vaccinia virus system [2].
• To study the DNA-binding properties of the murine homeodomain-containing protein, Hox-2.3, a hybrid expression system was used, combining gene expression by recombinant vaccinia virus (reVV) with bacteriophage T7 transcription [2].
• A transgenic mouse (Hoxb7/GFP) in which enhanced green fluorescent protein (GFP) is expressed in CDs was bred with an ARPKD mouse (BPK), and GFP-positive cells from normal and cystic mice were selected by fluorescence-activated cell sorting [3].

High impact information on Hoxb7

• To study the differential activities of the two RET isoforms further, we generated transgenic mice expressing ligand-dependent and constitutively active forms of RET9 or RET51 under the control of the Hoxb7 regulatory sequences [4].
• They derive from the Hox 1.1, Hox 2.3, Hox 6.1 genes and two previously undescribed genes, one of a type (paired) not found before in vertebrates [5].
• LoxP sites were inserted into AQP2 introns 2 and 3, and transgenic mice were bred with strains expressing Cre recombinase under the control of CD-specific Hoxb7- or global EIIa promoter [6].
• Expression of a Hoxb7/RET-PTC2 transgene, encoding a ligand-independent form of RET kinase, caused the development of abnormal nodules, outside the kidney or at its periphery, containing branched epithelial tubules apparently formed by deregulated growth of the ureteric bud [7].
• We show that elements driving A-P restricted gene expression are located within the 3.5 kb proximal upstream sequences of the Hoxb-7 gene [8].

Biological context of Hoxb7

• Together the 3.5 kb sequences proximal to Hoxb-7 mediate A-P restricted Hoxb-7/lacZ gene expression in a domain showing rostral boundaries more posterior than those of Hoxb-7 [8].
• 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 [9].
• In vivo ureteric branching morphogenesis in Hoxb7/GFP mice was also analyzed [10].
• The mouse Hox-2.3 gene contains an Antp-like homeobox sequence and is expressed in a spatially restricted anteroposterior domain during development [11].
• 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 [11].

Anatomical context of Hoxb7

• Analysis of Hoxa7/Hoxb7 mutants suggests periodicity in the generation of the different sets of vertebrae [12].
• Co-infected HeLa cells produced large amounts of full-length Hox-2.3 protein [2].
• The transgene apparently lacks sequences needed for correct Hox-2.3 expression in somitic and lateral plate mesoderm and in neurectoderm [11].
• Using in situ hybridization, we first detect Hox-2.3 transcripts in the allantois primordium at 7.5 days post coitum (p.c.). One day later transcripts are found in embryonic ectoderm and mesoderm [13].
• In 9.5- and 10.5- day embryos Hox-2.3 expression is observed in the central nervous system (CNS) from a rostral boundary in the upper spinal cord to the caudal end [13].

Associations of Hoxb7 with chemical compounds

• Hox-2.3, MM-3, and HuC1 also share a stretch of six glutamic acid residues followed by a stop codon 15-20 amino acids 3' of the homeo domain [14].
• Embryonic day 11.5 metanephroi were microdissected from Hoxb7-green fluorescence protein mice and grown for 48 h in serum-free medium in the presence or absence of Ang II [15].
• Hox 2.3 was also super-induced by serum, in the presence of cycloheximide, in cells rested previously in serum-free media, suggesting that new protein synthesis was not required for expressive augmentation [16].

Other interactions of Hoxb7

• When crossed to RET knockout mice, the Hoxb7/RET transgene, which encoded the RET9 isoform, supported normal kidney development in some RET-/- animals, indicating that the other major isoform, RET51, is not required in this organ [7].
• The induction of Hox 2.3, moreover, was not specific for tubular epithelium, since the gene could be activated in tubulointerstitial fibroblasts after treatment with EGF [16].
• This study reports the expression pattern of the murine homeobox-containing gene Hox-2.3 during development [13].
• Treatment of the cells to Hox 2.3 antisense oligodeoxynucleotides led to a selective inhibition of myeloid colony formation, both in size and in numbers, but without significant effect on erythroid and megakaryocytic haematopoiesis [17].
• This AP expression pattern is distinct from those reported for the expression of GD3, nestin, Hox 2.3, and Wnt-1 during brain development [18].

References