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

doi:10.1038/ng.138

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

Urology

Research output: Contribution to journal › Article › peer-review

421 Scopus citations

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.

Original language	English (US)
Pages (from-to)	751-760
Number of pages	10
Journal	Nature Genetics
Volume	40
Issue number	6
DOIs	https://doi.org/10.1038/ng.138
State	Published - Jun 1 2008

Access

10.1038/ng.138

Fingerprint Dive into the research topics of 'Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model'. Together they form a unique fingerprint.

Cite this

Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. / Stark, Kimberly L.; Xu, Bin; Bagchi, Anindya; Lai, Wen Sung; Liu, Hui; Hsu, Ruby; Wan, Xiang; Pavlidis, Paul; Mills, Alea A.; Karayiorgou, Maria; Gogos, Joseph A.

In: Nature Genetics, Vol. 40, No. 6, 01.06.2008, p. 751-760.

Research output: Contribution to journal › Article › peer-review

@article{0847db90f5254e20b7cc675dc7c3e371,

title = "Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model",

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.",

author = "Stark, {Kimberly L.} and Bin Xu and Anindya Bagchi and Lai, {Wen Sung} and Hui Liu and Ruby Hsu and Xiang Wan and Paul Pavlidis and Mills, {Alea A.} and Maria Karayiorgou and Gogos, {Joseph A.}",

year = "2008",

month = jun,

day = "1",

doi = "10.1038/ng.138",

language = "English (US)",

volume = "40",

pages = "751--760",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model

AU - Stark, Kimberly L.

AU - Xu, Bin

AU - Bagchi, Anindya

AU - Lai, Wen Sung

AU - Liu, Hui

AU - Hsu, Ruby

AU - Wan, Xiang

AU - Pavlidis, Paul

AU - Mills, Alea A.

AU - Karayiorgou, Maria

AU - Gogos, Joseph A.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=43949124669&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43949124669&partnerID=8YFLogxK

U2 - 10.1038/ng.138

DO - 10.1038/ng.138

M3 - Article

C2 - 18469815

AN - SCOPUS:43949124669

VL - 40

SP - 751

EP - 760

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 6

ER -