Ataxia-telangiectasia (A-T) is caused by the loss of function of the ATM gene, usually as a heterozygotic combination of two allelic mutations. In most cases, ATM mutations lead to expression of truncated proteins through early termination, but there are a large number of variations in mutation sites (Concannon and Gatti, 1997, Jacquemin et al., 2012). Studies of functional properties of A-T missense mutations found varying ATM protein levels and abnormal enrichment of cytoplasmic ATM protein (Jacquemin et al., 2012). Mouse models of A-T have been limited to standard knockout strategies that are normally homozygotic (Barlow et al., 1996, Xu et al., 1996). Because mutations may lead to expression of a portion of the ATM protein or even a full-length ATM protein lacking key regulatory sites, there is a possibility of partial function or dominant-negative function in A-T. For this reason, we sought to develop a collection of human A-T induced pluripotent stem cells (iPSC) for functional studies.
