Welcome! Click here to login or here to register.
 |
|||||||||||||||||||
|
|||||||||||||||||||
 |
|||||||||||||||||||
"An essential function for NBS1 in the prevention of ataxia and cerebellar defects." |
Frappart PO, Tong WM, Demuth I, Radovanovic I, Herceg Z, Aguzzi A, Digweed M, Wang ZQ |
Published May 1, 2005 in Nat Med volume 11 .
Pubmed ID: 15821748
Abstract:
| Nijmegen breakage syndrome (NBS), ataxia telangiectasia and ataxia telangiectasia-like disorder (ATLD) show overlapping phenotypes such as growth retardation, microcephaly, cerebellar developmental defects and ataxia. However, the molecular pathogenesis of these neurological defects remains elusive. Here we show that inactivation of the Nbn gene (also known as Nbs1) in mouse neural tissues results in a combination of the neurological anomalies characteristic of NBS, ataxia telangiectasia and ATLD, including microcephaly, growth retardation, cerebellar defects and ataxia. Loss of Nbn causes proliferation arrest of granule cell progenitors and apoptosis of postmitotic neurons in the cerebellum. Furthermore, Nbn-deficient neuroprogenitors show proliferation defects (but not increased apoptosis) and contain more chromosomal breaks, which are accompanied by ataxia telangiectasia mutated protein (ATM)-mediated p53 activation. Notably, depletion of p53 substantially rescues the neurological defects of Nbn mutant mice. This study gives insight into the physiological function of NBS1 (the Nbn gene product) and the function of the DNA damage response in the neurological anomalies of NBS, ataxia telangiectasia and ATLD. |
This publication refers to following REPAIRtoire entries:
| Genes |
Last modification of this entry: Oct. 6, 2010
Add your own comment!
There is no comment yet.
|
|
|
|