Disease relevance of hy1

• Defects in cilia are associated with several human disorders, including Kartagener syndrome, polycystic kidney disease, nephronophthisis and hydrocephalus [1].
• Mutations in the human L1 gene are associated with a variable phenotype, including mental retardation and anomalous development of the nervous system, referred to as 'CRASH' (corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus) [2].
• Hydrocephalus is a common and potentially devastating birth defect affecting the CNS, and its relationship with G protein-coupled receptors (GPCRs) is unknown [3].
• Mental retardation, hydrocephalus, and agenesis of the corpus callosum are observed both in fetal alcohol syndrome (FAS) and in children with mutations in the gene for the cell adhesion molecule L1 [4].
• Rare surviving homozygous Nfia(-/-) mice lack a corpus callosum, show severe communicating hydrocephalus, a full-axial tremor indicative of neurological defects, male-sterility, low female fertility, but near normal life spans [5].

Psychiatry related information on hy1

• Two subpopulations were distinguished: (i) 70% of mice underwent a rapidly progressive hydrocephalus and died during the first 2 months of life; they presented macrocephaly, extremely large expansion of the ventricles, equilibrium impairment and decreased motor activity [6].
• Those mice in the severe hydrocephalus group were poorer in a nonspatial discrimination learning task, had less paw asymmetry, and were less active in a swimming task [7].
• Clinical studies have shown that infants who experience germinal matrix hemorrhage can develop hydrocephalus or suffer from long-term neurologic dysfunction, including cerebral palsy, seizures, and learning disabilities [8].

High impact information on hy1

• The hyh (hydrocephalus with hop gait) mouse shows a markedly small cerebral cortex at birth and dies postnatally from progressive enlargement of the ventricular system [9].
• In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death [10].
• We show that congenital hydrocephalus involves a point mutation in Mf1, generating a truncated protein lacking the DNA-binding domain [11].
• Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production [12].
• Remarkably, Tg mice developed dose-dependent hydrocephalus-like characteristics, including enlarged third and lateral ventricles and reduced cerebral cortex, corpus callosum, and subcommissural organ (SCO) [3].

Chemical compound and disease context of hy1

• Following a single intraperitoneal injection of 6-aminonicotinamide (6-AN, 50 mg/kg of body weight) into newborn mice of the Institute of Cancer Research strain, hydrocephalus consistently developed nine days after injection, with rapid progression [13].
• OBJECT: The authors investigated the effects of heavy water (D2O) on intrameningeal fibrosis and on the expression of cytokine production in mice with kaolin-induced hydrocephalus [14].
• Evident malformations resulting from cyclophosphamide application were those of the head (hydrocephalus, exencephalus, exophthalmus, median cleft palate, micrognathia), of the extremities (syndactylia, polydactylia), caudal malformation (stunted and crooked tail) and an overall developmental retardation of the fetuses [15].
• Adult B10.PL-derived immunological genes knockout mice injected with 100 microg lipopolysaccharide (LPS) showed severe hydrocephalus and meningitis [16].

Biological context of hy1

• Neuronal proliferation and apoptosis were implicated in hydrocephalus, and we observed significantly reduced neuronal proliferation and massively increased neuronal apoptosis in the developing cortex and SCO of Tg embryos, while neurite outgrowth and neuronal migration in vitro remain uncompromised [3].
• Heterozygotes showed an increased tendency to intrauterine death with some fetuses having incomplete neural tube closure and some live-born heterozygotes developing hydrocephalus [17].
• More than 60% of B(DeltaI)/B(-) mice developed overt hydrocephalus and showed more severe defects in neural cell migration and adhesion than did B(DeltaI)/B(DeltaI) mice [18].
• Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6 [19].
• One line of mice harboring a cardiac-specific epoxygenase transgene developed head swelling and rapid neurological decline in young adulthood, and had marked hydrocephalus of the lateral and third ventricles [20].

Anatomical context of hy1

• These neoplasms consist of aggressive fibrosarcomas of soft tissue as well as diffuse meningeal tumors originating from the dura mater that surround the whole central nervous system and cause severe hydrocephalus [21].
• Pol lambda(-/-) mice develop hydrocephalus with marked dilation of the lateral ventricles and exhibit a high rate of mortality after birth, although embryonic development appears normal [22].
• Structurally altered basement membranes and hydrocephalus in a type XVIII collagen deficient mouse line [23].
• Ultrastructural analysis reveals that inner dynein arms of cilia from both the ependymal cell layer and respiratory epithelium are defective, which may underlie the pathogenesis of hydrocephalus, situs inversus totalis, chronic sinusitis, and male infertility [22].
• Comparison with the phenotype of Wnt1(sw/sw) (swaying) mutants suggests that subcommissural organ failure is the main cause of prenatal hydrocephalus observed in both strains [24].

Associations of hy1 with chemical compounds

• Loss of the serine/threonine kinase fused results in postnatal growth defects and lethality due to progressive hydrocephalus [25].
• Ethylenethiourea (ETU) is a specific neuroteratogen that induces communicating hydrocephalus ex vacuo at oral doses far lower than those that cause any observable toxic sign or 50% death (LD50) in the rat dam [26].
• 6-Aminonicotinamide-induced hydrocephalus in suckling mice [13].
• When the mice were immunosuppressed with cyclophosphamide, they ceased to develop hydrocephalus [27].
• Hydrocephalus following prenatal methylmercury poisoning [28].

Regulatory relationships of hy1

• Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation [29].

Other interactions of hy1

• An unexpected finding is that the modified Apob allele is strongly associated with exencephalus and hydrocephalus [30].
• Development of hydrocephalus in mice lacking SOCS7 [31].
• We show here that in a specific C57BL background, 20% of the Col18a1(-/-) mice developed hydrocephalus, and dilation of the brain ventricles was observed by MRI in all of the mutant mice [23].
• Msx1-deficient mice fail to form prosomere 1 derivatives, subcommissural organ, and posterior commissure and develop hydrocephalus [32].
• The development of spontaneous hydrocephalus in mouse models resulting from the overexpression of transforming growth factor-beta (TGFbeta-1) has been previously described, although the mechanism by which this occurs remains obscure [33].

Analytical, diagnostic and therapeutic context of hy1

• Insights into the pathogenesis of hydrocephalus from transgenic and experimental animal models [34].
• Ovary transplantation from an affected female founder has permitted perpetuation of one of the lines as a hydrocephalus model whose genetic defect is known [35].
• The pathogenesis of hydrocephalus following reovirus type 1 inoculation of neonatal mice has been examined by light microscopy, radiology, immunofluorescence, and electron microscopy [36].
• Induction of communicating hydrocephalus in mice by intrathecal injection of human recombinant transforming growth factor-beta 1 [37].
• The living shunt: a tissue engineering approach in the treatment of hydrocephalus [38].

References