Journal ArticleDOI
Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model
Kimberly L. Stark,Bin Xu,Anindya Bagchi,Wen-Sung Lai,Hui Liu,Ruby Hsu,Xiang Wan,Paul Pavlidis,Alea A. Mills,Maria Karayiorgou,Joseph A. Gogos +10 more
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TLDR
Evidence is provided that the abnormal miRNA biogenesis emerges because of haploinsufficiency of the Dgcr8 gene, which encodes an RNA-binding moiety of the 'microprocessor' complex and contributes to the behavioral and neuronal deficits associated with the 22q11.2 microdeletion.Abstract:
Individuals with 22q11.2 microdeletions show behavioral and cognitive deficits and are at high risk of developing schizophrenia. We analyzed an engineered mouse strain carrying a chromosomal deficiency spanning a segment syntenic to the human 22q11.2 locus. We uncovered a previously unknown alteration in the biogenesis of microRNAs (miRNAs) and identified a subset of brain miRNAs affected by the microdeletion. We provide evidence that the abnormal miRNA biogenesis emerges because of haploinsufficiency of the Dgcr8 gene, which encodes an RNA-binding moiety of the 'microprocessor' complex and contributes to the behavioral and neuronal deficits associated with the 22q11.2 microdeletion.read more
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22q11.2 deletion syndrome
Donna M. McDonald-McGinn,Kathleen E. Sullivan,Bruno Marino,Nicole Philip,Ann Swillen,Jacob A. S. Vorstman,Elaine H. Zackai,Beverly S. Emanuel,Joris Vermeesch,Bernice E. Morrow,Peter J. Scambler,Anne S. Bassett +11 more
TL;DR: The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease as mentioned in this paper.
Journal ArticleDOI
Dendritic spine pathology in neuropsychiatric disorders
TL;DR: This work discusses recent neuropathological, genetic, molecular and animal model studies that implicate structural alterations at spiny synapses in the pathogenesis of major neurological disorders, focusing on ASD, schizophrenia and Alzheimer's disease as representatives of these categories across different ages of onset.
Journal ArticleDOI
MicroRNAs in development and disease.
Danish Sayed,Maha Abdellatif +1 more
TL;DR: The discovery, structure, and mode of function of miRNAs in mammalian cells are described, before elaborating on their roles and significance during development and pathogenesis in the various mammalian organs, while attempting to reconcile their functions with the existing knowledge of their targets.
Journal Article
The 22q11.2 deletion syndrome.
TL;DR: 22q11.2 deletion syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome.
Journal ArticleDOI
Strong association of de novo copy number mutations with sporadic schizophrenia.
TL;DR: The results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease.
References
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Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP.
Guoping Feng,Rebecca H. Mellor,Michael L. Bernstein,Cynthia Keller-Peck,Quyen T. Nguyen,Mia Wallace,Jeanne M. Nerbonne,Jeff W. Lichtman,Joshua R. Sanes +8 more
TL;DR: Each of 25 independently generated transgenic lines expressed XFP in a unique pattern, even though all incorporated identical regulatory elements (from the thyl gene), for example, all retinal ganglion cells or many cortical neurons were XFP positive in some lines, whereas only a few ganglions or only layer 5 cortical pyramids were labeled in others.
Journal ArticleDOI
Differential Contribution of Amygdala and Hippocampus to Cued and Contextual Fear Conditioning
R. G. Phillips,Joseph E. LeDoux +1 more
TL;DR: An associative roles for the amygdala and a sensory relay role for the hippocampus are suggested in fear conditioning, which is involved in the conditioning of fear responses to simple, modality-specific conditioned stimuli as well as to complex, polymodal stimuli.