Monckton, D.G., Coolbaugh, M.I., Ashizawa, K.T., Siciliano, M.J., and Caskey, C.T. (1997) Hypermutable myotonic dystrophy CTG repeats in transgenic mice. Nature Genetics, 15 (2). 193 -196. ISSN 1061-4036 (doi:10.1038/ng0297-193)
Full text not currently available from Enlighten.
Publisher's URL: http://dx.doi.org/10.1038/ng0297-193
Myotonic dystrophy (DM) is one of a growing number of inherited human disorders associated with the expansion of triplet repeat DNA sequences. Expanded alleles are highly unstable in both the germline and soma, accounting in large part for the unusual genetics of this disorder, its phenotypic variability and probably, the progressive nature of the symptoms. However, the molecular mechanisms and the genetic factors modulating repeat stability in DM and the other human disorders associated with expanded repeats are not well understood. To provide a model system in which the turnover of triplet repeats could be studied throughout mammalian development, we have generated five transgenic mouse lines incorporating expanded CTG/CAG arrays derived from the human DM locus. Transgene analysis has revealed germline hypermutability, including expansions, deletions and parent-of-origin effects, somatic and early embryonic instability and segregation distortion. Mutational differences between lines and sexes demonstrate that stability, as in humans, is modulated by as yet unidentified cis and trans acting genetic elements.
|Glasgow Author(s):||Monckton, Prof Darren|
|Authors:||Monckton, D.G., Coolbaugh, M.I., Ashizawa, K.T., Siciliano, M.J., and Caskey, C.T.|
|Subjects:||Q Science > QH Natural history > QH426 Genetics|
|College/School:||College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology|
|Journal Name:||Nature Genetics|