Disease relevance of Atrx

• To better understand the role of ATRX in development and the associated abnormalities in the ATR-X (alpha thalassemia mental retardation, X-linked) syndrome, we conditionally inactivated the homolog in mice, Atrx, at the 8- to 16-cell stage of development [1].

High impact information on Atrx

• Here, we used a conditional gene-targeting approach to inactivate Atrx, specifically in the forebrain of mice [2].
• Moreover, cortical progenitors isolated from Atrx-null mice undergo enhanced apoptosis upon differentiation [2].
• All these parameters of SHM were unaltered in memory and GC B cells lacking one or both Rad54 paralogues [3].
• Furthermore, although MMC-stimulated sister chromatid exchange (SCE) was suppressed in the Rad54-deficient ALT ES cells, ALT-associated telomere SCE was not affected [4].
• Although Rad54-deficient ALT ES cells showed radiosensitivity in line with expectation, cell growth and telomeres were maintained for more than 200 cell divisions [4].

Biological context of Atrx

• The Dnmt3l protein contains an ADD zinc finger, which Dnmt3l shares with other Dnmt3 family members and Atrx [5].
• Loss of Atrx affects trophoblast development and the pattern of X-inactivation in extraembryonic tissues [1].
• Together these findings demonstrate an unexpected, specific, and essential role for Atrx in the development of the murine trophoblast and present an example of escape from imprinted X chromosome inactivation [1].

Anatomical context of Atrx

• Cells deleted for Brca2 exon 27 are hypersensitive to gamma-radiation, streptonigrin, mitomycin C and camptothecin and mildly resistant to ICRF-193 which is similar to HR defective cells null for Rad54 [6].
• Knockout mice for the ATR2 gene show a significant incidence of congenital urinary tract anomalies [7].

References