Cloning, characterization and genetic analysis of the Hmx genes, a novel homeobox gene family required for sensory organ development and maternal reproduction.
Item
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Title
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Cloning, characterization and genetic analysis of the Hmx genes, a novel homeobox gene family required for sensory organ development and maternal reproduction.
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Identifier
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AAI9820589
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identifier
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9820589
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Creator
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Wang, Weidong.
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Contributor
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Adviser: Thomas Lufkin
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Date
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1998
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Neuroscience
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Abstract
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Three novel homeobox genes were isolated, one from Drosophila melanogaster (Drosophila Hmx gene) and two from mouse (murine Hmx2 and Hmx3). The striking similarity between the homeodomains of these three genes and the previously identified genes, TgHbox5, gH6, human H6 as well as recently cloned mouse Hmx1 gene together with the low level identity to other homeobox genes indicate that the Hmx genes are a novel gene family.;Hmx1 is assigned to the proximal region of mouse Chromosome 5. Hmx2 and Hmx3 are closely linked on the distal region of mouse Chromosome 7. In addition to their similar expression in the central and peripheral nervous systems, Hmx2 and Hmx3 show identical expression patterns in sensory organ related structures. Hmx3 is one of the earliest markers for vestibular inner ear development, and is also up-regulated in the myometrium of the uterus during pregnancy. Mice lacking Hmx3 exhibit abnormal circling behavior owing to severe vestibular defects. Histological analysis indicates a depletion of sensory cells in the saccule and utricle, and a complete loss of the horizontal semicircular canal crista, as well as a fusion of the utricle and saccule endolymphatic spaces into a common utriculosaccular cavity of these Hmx3 null mice. The majority of Hmx3 null females are infertile, even though they show normal ovulation and fertilization. Embryos fail to implant successfully in the Hmx3 null uterus and subsequently die. Transfer of preimplantation embryos from Hmx3 null uterine horns to wildtype pseudopregnant females results in successful pregnancy, indicating a failure of the Hmx3 null uterus to support normal post-implantation development of the embryos. Molecular analysis reveals a perturbation in Hmx, Wnt and LIF gene expression in the Hmx3 null uterus. Interestingly, expression of both Hmx1 and Hmx2 is down-regulated in the Hmx3 null uterus, suggesting a regulatory hierarchy exists among the Hmx genes during pregnancy.;Mice carrying disrupted Hmx2 and Hmx3 genes display a more severe phenotype than Hmx3 null mice. The double knockout results in perinatal lethality. The few surviving offspring show a complete loss of balance, severe developmental retardation and premature death.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
