RGD Reference Report - BRCA2 is required for neurogenesis and suppression of medulloblastoma. - Rat Genome Database

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BRCA2 is required for neurogenesis and suppression of medulloblastoma.

Authors: Frappart, PO  Lee, Y  Lamont, J  McKinnon, PJ 
Citation: Frappart PO, etal., EMBO J. 2007 Jun 6;26(11):2732-42. Epub 2007 May 3.
RGD ID: 11038793
Pubmed: PMID:17476307   (View Abstract at PubMed)
PMCID: PMC1888666   (View Article at PubMed Central)
DOI: DOI:10.1038/sj.emboj.7601703   (Journal Full-text)

Defective DNA damage responses in the nervous system can result in neurodegeneration or tumorigenesis. Despite the importance of DNA damage signalling, the neural function of many critical DNA repair factors is unclear. BRCA2 is necessary for homologous recombination repair of DNA and the prevention of diseases including Fanconi Anemia and cancer. We determined the role of BRCA2 during brain development by inactivating murine Brca2 throughout neural tissues. In striking contrast to early embryonic lethality after germ-line inactivation, Brca2(LoxP/LoxP);Nestin-cre mice were viable. However, Brca2 loss profoundly affected neurogenesis, particularly during embryonic and postnatal neural development. These neurological defects arose from DNA damage as Brca2(LoxP/LoxP);Nestin-cre mice showed extensive gammaH2AX in neural tissue and p53 deficiency restored brain histology but lead to rapid formation of medulloblastoma brain tumors. In contrast, loss of the Atm kinase did not markedly attenuate apoptosis after Brca2 loss, but did partially restore cerebellar morphology, supporting a genomic surveillance function for ATM during neurogenesis. These data illustrate the importance of Brca2 during nervous system development and underscore the tissue-specific requirements for DNA repair factors.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
medulloblastoma  ISOBrca2 (Mus musculus)11038793; 11038793 RGD 
medulloblastoma  IMP 11038793 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Brca2  (BRCA2, DNA repair associated)

Genes (Mus musculus)
Brca2  (breast cancer 2, early onset)

Genes (Homo sapiens)
BRCA2  (BRCA2 DNA repair associated)


Additional Information