Disease relevance of xn

• In agreement with these findings, Ski-/- mice display a cranial neural tube defect that results in exencephaly and a marked reduction in skeletal muscle mass [1].
• Through the genesis of Meg2-deficient mice, we demonstrate that Meg2-/- embryos manifest hemorrhages, neural tube defects including exencephaly and meningomyeloceles, cerebral infarctions, abnormal bone development, and >90% late embryonic lethality [2].
• Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain [3].
• The neural tube defects observed include both exencephaly and spina bifida, and the phenotype exhibits partial penetrance with about 60% of homozygous embryos developing neural tube defects [4].
• These animals die perinatally and exhibit varying combinations of gross developmental defects throughout the second half of development, including acrania, exencephaly, cleft palate, limb abnormalities and omphalocele [5].

High impact information on xn

• Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator [6].
• Here we show that Cited2-/- embryos die with cardiac malformations, adrenal agenesis, abnormal cranial ganglia and exencephaly [6].
• Gadd45a-null mice generated by gene targeting exhibited several of the phenotypes characteristic of p53-deficient mice, including genomic instability, increased radiation carcinogenesis and a low frequency of exencephaly [7].
• Homozygous mutant mice show perinatal lethality resulting from exencephaly, a defect caused by failed closure of the cranial neural tube during neurulation [8].
• The splotch (Sp) mouse mutant displays defects in neural tube closure in the form of exencephaly and spina bifida [9].

Chemical compound and disease context of xn

• Splotch is an established model of folate-sensitive neural tube defects, and homozygous mutant embryos develop spina bifida and sometimes exencephaly [10].
• In all cases, the rates of exencephaly, embryolethality, and fetal weight retardation induced by the methyl-branched derivatives were very low when compared to those of the parent compounds [11].
• Also, the type of these malformations was different from those (exencephaly, cleft palate and macroglossia) induced by a known teratogenic dose of vitamin A (1,200,000 IU) [12].
• Teratogenicity studies performed in a SWV/Fnn-mouse model for VPA-induced-exencephaly showed that on the equimolar basis OM-TMCD possesses the same fetal toxicity and ability to induce NTDs as VPA, but since OM-TMCD is a much more potent anticonvulsant its activity/exencephaly formation ratio appears to be much more beneficial than that of VPA [13].
• The higher dose of methionine did not produce a particularly beneficial effect on embryonic survival, fetal body weight and occurrence of exencephaly [14].

Biological context of xn

• Inheritance and morphology of exencephaly, a neonatal lethal recessive with partial penetrance, in the house mouse [15].
• Cited2(-/-) mutants died at late gestation and exhibited heart defects and exencephaly, arising from defective closure of the midbrain (MB) and hindbrain [16].
• The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice [17].
• LMO4 mutant mice die embryonically and exhibit exencephaly, which is associated with abnormal patterns of cell proliferation and with high levels of apoptotic cell death within the neuroepithelium [18].
• A small interval was identified that, when hemizygous, caused specific embryonic lethal phenotypes (exencephaly and edema) in most fetuses [19].

Anatomical context of xn

• Tcof1 heterozygous mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia [20].
• Matings involving the Sp allele yielded litters with significantly higher percentages of maternal diabetes-induced spina bifida aperta but not exencephaly, and this increase was shown to be associated with the presence of a single copy of the Sp allele in affected fetuses [21].
• The exencephaly is due to a primary failure of neurulation, resulting from a lack of mid/hindbrain dorsolateral hinge point (DLHP) formation [22].
• Targeted mutation of the mouse laminin alpha 5 gene Lama5 causes embryonic lethality at E14-E17 associated with exencephaly, syndactyly, placentopathy, and kidney defects, all attributable to abnormal basement membranes [23].
• Lymphocytes from adult mice bearing a known difference in genetic susceptibility to teratogen-induced exencephaly (SWV/SD, and DBA/2J) were evaluated for changes in protein synthesis following an in vivo heat treatment [24].

Associations of xn with chemical compounds

• FA supplementation reduced the recurrence risk of Cd exencephaly by as much as 55% [25].
• Propyl-4-yn-valproic acid (2-propyl-4-pentynoic acid), an analogue of valproic acid with a triple bond in one alkyl side chain, potently induces exencephaly in mice [26].
• The low dose of methionine only numerically reduced the spontaneous exencephaly [14].
• Effect of L-threonine on trypan blue-induced exencephaly [27].
• Although these anomalies were similar to the minor defects seen in the fetuses of morphine sulfate-treated mice, the major anomalies such as exencephaly, cryptorchid testes, and rib and vertebral fusions produced by morphine were not present in the fetuses of mice challenged with codeine [28].

Regulatory relationships of xn

• RESULTS: Folbp2(-/-) mice had higher VPA-induced frequencies of embryonic lethality and exencephaly than did the wild-type control mice during folate supplementation and a control diet, respectively [29].

Other interactions of xn

• In addition to craniofacial and urogenital anomalies, severe axial skeletal malformations were found to be consistently associated with exencephaly [30].
• In the mouse, the gene mutation Splotch (Sp) causes a pigmentation defect in heterozygotes while homozygotes have spina bifida +/- exencephaly [31].
• However, exencephaly, low set ears, cleft palate and ventricular septal defect were observed only in both aerosol-exposed groups (whole-body and nose-only exposed) [32].
• If heterozygote Ts/+ mothers are mated with normal-tail +/+ males and are treated with teratogenic doses of trypan blue on the eighth day of pregnancy, the mutant F1 heterozygotes develop exencephaly, folded neural tube and spina bifida significantly more often than non-mutants [33].

Analytical, diagnostic and therapeutic context of xn

• Sensitivity to hyperthermia-induced exencephaly is recessive to resistance in these crosses [24].
• VPA-induced exencephaly in mice may provide an animal model to further investigate biochemical markers for prenatal diagnosis of neural tube defects [34].
• Folinic acid, whether administered by intraperitoneal injection or in osmotic mini-pumps, did not decrease the number of mouse fetuses with VPA-induced exencephaly [35].
• The genetic cause of this exencephaly was investigated in a cross to a normal related ICR/Bc strain and in subsequent classical genetic crosses (F2, first and second backcrosses) [36].
• In addition to reducing VA-induced exencephaly, immunostimulation with FCA resulted in fetal mice displaying anury (absence of tails) [37].

References