Alternative titles; symbols
HGNC Approved Gene Symbol: HMX2
Cytogenetic location: 10q26.13 Genomic coordinates (GRCh38): 10:123,148,136-123,150,672 (from NCBI)
Homeobox-containing genes represent a major class of transcription factors directly involved in the regulation of embryogenesis. Most mammalian homeobox-containing genes reside in 4 distinct HOX clusters (A through D) comprising at least 38 individual genes in 13 paralogous subgroups (Garcia-Fernandez and Holland, 1994). Outside the 4 HOX clusters, more than 25 additional homeobox-containing genes have been reported in both vertebrate and invertebrate species. Stadler et al. (1995) identified novel members of the nonclustered H6 family in mouse, horse, chicken, fish, lamprey, sea urchin, sheep, fruit fly, and human. Genes of this family are highly conserved at both the nucleotide and amino acid levels in the diverse species. In addition to the human homeobox gene H6 (142992), they identified a human H6-like sequence, HMX2.
Wang et al. (2000) cloned mouse Hmx2, which encodes a deduced 263-amino acid protein with a C-terminal homeodomain. Both Hmx2 and Hmx3 (613380) were expressed in mouse at embryonic day 9.5 in the rostral half of the otic vesicle and in the cleft between the first and second branchial arches. By embryonic day 10.5, both genes were expressed in discrete regions of the central nervous system and in sensory epithelia of the tongue and nasal cavity. Both genes were also expressed in the uterus during pregnancy.
Wang et al. (2001) found that Hmx2 was expressed in both sensory and nonsensory epithelia of all 3 semicircular canals, endolymphatic sac, utricle, and saccule at day 13.5 of mouse embryo development. At embryonic day 14.5, Hmx2 was expressed in the stria vascularis of the cochlea.
Stadler et al. (1995) mapped the HMX2 gene to chromosome 10q25.2-q26.3 by studies of human/rodent monochromosomal hybrids and of a somatic cell panel containing well-characterized deletions and rearrangements of chromosome 10.
Stadler et al. (1995) noted that extensive studies of the clustered and nonclustered homeobox genes suggest that the former evolved by local duplications of a single ancestral gene followed by larger duplications of chromosomal regions, whereas nonclustered homeobox genes, such as the H6 homeobox genes, appear to be derived by smaller gene duplication events followed by sequence divergence within the duplications of larger chromosomal regions.
Wang et al. (2001) found that the majority of Hmx2 -/- mice displayed hyperactivity, head tilting, and circling behavior. Hmx2 -/- mice had variable inner ear defects, including gross dysgenesis of all 3 semicircular ducts, but the endolymphatic duct/sac and cochlear duct appeared normal. Hmx2 -/- mice showed progressive impairment of the sensory system of the inner ear, including reduced number of sensory hair cells, reduced number of vestibular ganglion neurons, and failure of otic epithelium and periotic mesenchymal cells to proliferate. Wang et al. (2001) also observed abnormal expression and patterning of genes critical for inner ear ontogeny, including Bmp4 (112262), Dlx5 (600028), and Pax2 (167409), in Hmx2 -/- mice.
Wang et al. (2004) found that Hmx2 +/- Hmx3 +/- compound heterozygous mice appeared normal and were fertile. Hmx2 -/- Hmx3 -/- double-knockout mice were born at the expected mendelian ratio and appeared normal, but they showed developmental delay, complete loss of balance, and muscle spasms, and most died around postnatal day 5. The vestibular system progressively degenerated in Hmx2 -/- Hmx3 -/- embryos. In addition, the hypothalamus and anterior pituitary were severely affected, and there was reduced expression of galanin (GAL; 137035) and reduced production of Ghrh (139190) and Gh (139250). Expression of Drosophila Hmx largely rescued these defects.
Garcia-Fernandez, J., Holland, P. W. H. Archetypal organization of the amphioxus Hox gene cluster. Nature 370: 563-566, 1994. [PubMed: 7914353] [Full Text: https://doi.org/10.1038/370563a0]
Stadler, H. S., Murray, J. C., Leysens, N. J., Goodfellow, P. J., Solursh, M. Phylogenetic conservation and physical mapping of members of the H6 homeobox gene family. Mammalian Genome 6: 383-388, 1995. [PubMed: 7647458] [Full Text: https://doi.org/10.1007/BF00355637]
Wang, W., Chan, E. K., Baron, S., Van de Water, T., Lufkin, T. Hmx2 homeobox gene control of murine vestibular morphogenesis. Development 128: 5017-5029, 2001. [PubMed: 11748138] [Full Text: https://doi.org/10.1242/dev.128.24.5017]
Wang, W., Grimmer, J. F., Van de Water, T. R., Lufkin, T. Hmx2 and Hmx3 homeobox genes direct development of the murine inner ear and hypothalamus and can be functionally replaced by Drosophila Hmx. Dev. Cell 7: 439-453, 2004. [PubMed: 15363417] [Full Text: https://doi.org/10.1016/j.devcel.2004.06.016]
Wang, W., Lo, P., Frasch, M., Lufkin, T. Hmx: an evolutionary conserved homeobox gene family expressed in the developing nervous system in mice and Drosophila. Mech. Dev. 99: 123-137, 2000. [PubMed: 11091080] [Full Text: https://doi.org/10.1016/s0925-4773(00)00488-3]