Expression of the transcription factor, TFII-I, during post-implantation mouse embryonic development

<p>Abstract</p> <p>Background</p> <p>General transcription factor (TFII-I) is a multi-functional transcription factor encoded by the Gtf2i gene, that has been demonstrated to regulate transcription of genes critical for development. Because of the broad range of genes regulated by TFII-I as well as its potential role in a significant neuro-developmental disorder, developing a comprehensive expression profile is critical to the study of this transcription factor. We sought to define the timing and pattern of expression of TFII-I in post-implantation embryos at a time during which many putative TFII-I target genes are expressed.</p> <p>Findings</p> <p>Antibodies to the N-terminus of TFII-I were used to probe embryonic mouse sections. TFII-I protein is widely expressed in the developing embryo. TFII-I is expressed throughout the period from E8-E16. However, within this period there are striking shifts in localization from cytoplasmic predominant to nuclear. TFII-I expression varies in both a spatial and temporal fashion. There is extensive expression in neural precursors at E8. This expression persists at later stages. TFII-I is expressed in developing lung, heart and gut structures. There is no evidence of isoform specific expression. Available data regarding expression patterns at both an RNA and protein level throughout development are also comprehensively reviewed.</p> <p>Conclusions</p> <p>Our immunohistochemical studies of the temporal and spatial expression patterns of TFII-I in mouse embryonic sections are consistent with the hypothesis that hemizygous deletion of <it>GTF2I </it>in individuals with Williams-Beuren Syndrome contributes to the distinct cognitive and physiological symptoms associated with the disorder.</p

Neurobiology of social behavior abnormalities in autism and Williams syndrome

Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities

Essential role of the N-terminal region of TFII-I in viability and behavior

<p>Abstract</p> <p>Background</p> <p><it>GTF2I </it>codes for a general intrinsic transcription factor and calcium channel regulator TFII-I, with high and ubiquitous expression, and a strong candidate for involvement in the morphological and neuro-developmental anomalies of the Williams-Beuren syndrome (WBS). WBS is a genetic disorder due to a recurring deletion of about 1,55-1,83 Mb containing 25-28 genes in chromosome band 7q11.23 including <it>GTF2I</it>. Completed homozygous loss of either the <it>Gtf2i </it>or <it>Gtf2ird1 </it>function in mice provided additional evidence for the involvement of both genes in the craniofacial and cognitive phenotype. Unfortunately nothing is now about the behavioral characterization of heterozygous mice.</p> <p>Methods</p> <p>By gene targeting we have generated a mutant mice with a deletion of the first 140 amino-acids of TFII-I. mRNA and protein expression analysis were used to document the effect of the study deletion. We performed behavioral characterization of heterozygous mutant mice to document <it>in vivo </it>implications of TFII-I in the cognitive profile of WBS patients.</p> <p>Results</p> <p>Homozygous and heterozygous mutant mice exhibit craniofacial alterations, most clearly represented in homozygous condition. Behavioral test demonstrate that heterozygous mutant mice exhibit some neurobehavioral alterations and hyperacusis or odynacusis that could be associated with specific features of WBS phenotype. Homozygous mutant mice present highly compromised embryonic viability and fertility. Regarding cellular model, we documented a retarded growth in heterozygous MEFs respect to homozygous or wild-type MEFs.</p> <p>Conclusion</p> <p>Our data confirm that, although additive effects of haploinsufficiency at several genes may contribute to the full craniofacial or neurocognitive features of WBS, correct expression of <it>GTF2I </it>is one of the main players. In addition, these findings show that the deletion of the fist 140 amino-acids of TFII-I altered it correct function leading to a clear phenotype, at both levels, at the cellular model and at the <it>in vivo </it>model.</p

Using Transcription Modules to Identify Expression Clusters Perturbed in Williams-Beuren Syndrome

The genetic dissection of the phenotypes associated with Williams-Beuren Syndrome (WBS) is advancing thanks to the study of individuals carrying typical or atypical structural rearrangements, as well as in vitro and animal studies. However, little is known about the global dysregulations caused by the WBS deletion. We profiled the transcriptomes of skin fibroblasts from WBS patients and compared them to matched controls. We identified 868 differentially expressed genes that were significantly enriched in extracellular matrix genes, major histocompatibility complex (MHC) genes, as well as genes in which the products localize to the postsynaptic membrane. We then used public expression datasets from human fibroblasts to establish transcription modules, sets of genes coexpressed in this cell type. We identified those sets in which the average gene expression was altered in WBS samples. Dysregulated modules are often interconnected and share multiple common genes, suggesting that intricate regulatory networks connected by a few central genes are disturbed in WBS. This modular approach increases the power to identify pathways dysregulated in WBS patients, thus providing a testable set of additional candidates for genes and their interactions that modulate the WBS phenotypes

result of propagation of sheep and goat pox viral vaccine strains into vero cells

Background: Sheep and goat pox viral disease, which affects negatively to our country’s economy by prevalence and infection, has high mortality and morbidity rate. Although our country manufactures sheep and goat pox viral vaccine using lamb’s testicle tissue in the Biocombinat (Bio-factory), in winter, there is high number of diseased animals, lamb testicle is scarce, therefore there is a need to produce cell-culture based sheep and goat pox vaccine.&#x0D; Materials and methods: Russian VNIIZJ strain type 2 sheep pox vaccine and Chinese goat pox live vaccine (serial number 010030) antigens were used after 20 times of dilution and propogated into Vero and BHK-21 cell culture. By PCR the result was examined and sequenced by ABI3130xl sequencer machine and sequences were compared by MEGA7 program&#x0D; Results: 3 days after infection sheep pox and 4 days after infection goat pox were shown CPE (cytopathic effect or cytopathogenic effect) respectively, 6 days after the infection both of them has been shown full CPE. From these infected materials we isolated viral DNA and run PCR assay using Biocombinat’s strain as a positive control. PCR products were all equal, 289 bp long. When we compare these DNA sequences of sheep and goat pox viruses, they were 92% identical to complete genome of Indian sheep and goat pox virus.&#x0D; Conclusion: We can produce cell-culture based live vaccine and diagnostic tests for sheep and goat pox viral disease by re-propagating these strains into Vero.&#x0D; Хонь, ямааны цэцгийн вирусын вакцины омгийг vero эсэд дасгасан дүн&#x0D; Хураангуй: Хонь, ямааны цэцгийн вируст өвчин халдвар, тархалт өндөртэй бөгөөд өвчлөл, хорогдлынтүвшин өндөр байгаа нь манай улсын эдийн засагт сөргөөр нөлөөлж байна. Манай улс Биокомбинат (Био-үйлдвэр) үйлдвэрт хонины цэцэг өвчний эсрэг вакциныг хурганы төмсөгний анхдагч эдэд өсгөвөрлөх замаар амьд вакцин, ямааны цэцэг өвчний эсрэг вакциныг ямаанд халдвар хийж ам, хамрын орчинд үүссэн шархны эдийг химийн бодисоор идэвхгүйжүүлэх замаар тус тус үйлдвэрлэж байна. Ялангуяа хонины цэцэг өвчний вакциныг зөвхөн мал төллөх хаврын цагт үйлдвэрлэх боломжтой байдаг нь өвлийн цагт гарсан өвчнийг хянах аргагүйд хүрч байна. Иймээс цаг хугацаанаас хамааралгүй вакцин үйлдвэрлэхэд дамжмал эсийн технологи хэрэглэх зайлшгүй шаардлагатай байна. Оросын VNIIZJ омогашигласан 2 төрлийн хонины цэцгийн амьд вакцин, Хятадын ямааны цэцгийн амьд вакцин (серийн дугаар 010030) шингэлж, Vero эсийн өсгөвөрт халдаасан. Стандарт ПГУ-аар үр дүнг шалгаж, ABI3130xl sequencer машинаар үүсгэгчийн нуклеотидын дарааллыг тодорхойлсон ба MEGA7 програмаар дарааллуудыг харьцуулж удам зүйн мод байгуулсан. Эсэд халдвар хийснээс 3 хоногийн дараа хонины цэцэг, 4 хоногийн дараа ямааны цэцэг CPE (cytopathic effect) буюу эс эмгэгшүүлэх нөлөө тус тус үзүүлсэн бөгөөд 6 хоногийн дараа хоёулаа бүрэн CPE үзүүлсэн байна. Эдгээр вирус агуулсан эсийн тэжээлт орчноос бид вирусын ДНХ ялгаж Биокомбинат-ын хонины цэцгийн Перего омгийг эерэг хяналт болгон ашиглаж ПГУ-ын шинжилгээг явуулсан. ПГУ-ын бүтээгдэхүүн бүгд адилхан, 289 хос суурийн урттай байсан. Хонь, ямааны цэцгийн вирусын ДНХ-ийн нуклеотидын дарааллыг харьцуулж үзэхэд хониныцэцгийн вирусын бүтэн геномтой 92%, ямааны цэцгийн вирусын бүтэн геномтой 90% адилханбайв. Бид эдгээр өвчний үүсгэгчийг Vero эсэд халдвар хийх нөхцлийг тогтворжуулсан ньдамжмал эсийн өсгөвөрт суурилсан амьд вакцины түүхий эдийг ихээр бэлтгэх боломжтойболлоо.&#x0D; Түлхүүр үг: эсийн өсгөвөр, эсийн эмгэгшил, днх дараалал, амьд вакцин</jats:p

Essential functions of the Williams-Beuren syndrome-associated TFII-I genes in embryonic development

GTF2I and GTF2IRD1 encoding the multifunctional transcription factors TFII-I and BEN are clustered at the 7q11.23 region hemizygously deleted in Williams-Beuren syndrome (WBS), a complex multisystemic neurodevelopmental disorder. Although the biochemical properties of TFII-I family transcription factors have been studied in depth, little is known about the specialized contributions of these factors in pathways required for proper embryonic development. Here, we show that homozygous loss of either Gtf2ird1 or Gtf2i function results in multiple phenotypic manifestations, including embryonic lethality; brain hemorrhage; and vasculogenic, craniofacial, and neural tube defects in mice. Further analyses suggest that embryonic lethality may be attributable to defects in yolk sac vasculogenesis and angiogenesis. Microarray data indicate that the Gtf2ird1 homozygous phenotype is mainly caused by an impairment of the genes involved in the TGFβRII/Alk1/Smad5 signal transduction pathway. The effect of Gtf2i inactivation on this pathway is less prominent, but downregulation of the endothelial growth factor receptor-2 gene, resulting in the deterioration of vascular signaling, most likely exacerbates the severity of the Gtf2i mutant phenotype. A subset of Gtf2ird1 and Gtf2i heterozygotes displayed microcephaly, retarded growth, and skeletal and craniofacial defects, therefore showing that haploinsufficiency of TFII-I proteins causes various developmental anomalies that are often associated with WBS