Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
Cancer Res ; 61(13): 4947-50, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11431321

ABSTRACT

Loss of imprinting (LOI) is the most common molecular abnormality in Wilms' tumor (WT), other embryonal cancers, and most other tumor types. LOI in WT involves activation of the normally silent maternal allele of the insulin-like growth factor-II (IGF2) gene, silencing of the normally active maternal allele of the H19 gene, and aberrant methylation of a differentially methylated region (DMR) upstream of the maternal copy of H19. Recently, the transcription factor CTCF, which binds to the H19 DMR, has been implicated in the maintenance of H19 and IGF2 imprinting. Here, we show that mutations in the CTCF gene or in the H19 DMR do not occur at significant frequency in WT, nor is there transcriptional silencing of CTCF. We also confirm that methylation of the H19 DMR in WT with LOI includes the CTCF core consensus site. However, some WTs with normal imprinting of IGF2 also show aberrant methylation of CTCF binding sites, indicating that methylation of these sites is necessary but not sufficient for LOI in WT.


Subject(s)
DNA Methylation , DNA-Binding Proteins/genetics , Genomic Imprinting , Insulin-Like Growth Factor II/genetics , Repressor Proteins , Transcription Factors/genetics , Wilms Tumor/genetics , Alleles , Base Sequence , Binding Sites , CCCTC-Binding Factor , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic , Humans , Mutation , RNA, Long Noncoding , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factors/metabolism
2.
J Clin Invest ; 106(12): 1447-55, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11120752

ABSTRACT

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.


Subject(s)
Deafness/genetics , Hyperplasia/genetics , Long QT Syndrome/genetics , Potassium Channels, Voltage-Gated , Potassium Channels/deficiency , Potassium Channels/metabolism , Stomach/pathology , Animals , Brain Stem/physiology , Cochlea/pathology , Cochlea/physiopathology , Deafness/physiopathology , Disease Models, Animal , Ear, Inner/pathology , Ear, Inner/physiopathology , Electrocardiography , Evoked Potentials, Auditory, Brain Stem , Female , Histocytochemistry , Humans , Hyperplasia/pathology , KCNQ Potassium Channels , KCNQ1 Potassium Channel , Locomotion/physiology , Male , Mice , Mice, Knockout , Mutation/genetics , Organ Size , Phenotype , Potassium Channels/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...