Mechanistic insight into the pathology of polyalanine expansion disorders revealed by a mouse model for X linked hypopituitarism

• Published in: PLoS genetics Vol. 9; no. 3; p. e1003290
• Main Authors: Hughes, James, Piltz, Sandra, Rogers, Nicholas, McAninch, Dale, Rowley, Lynn, Thomas, Paul
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2013; Public Library of Science (PLoS)
• Subjects: Aggregates; Alleles; Aniline; Animals; Biology; Cell culture; Cell Nucleus; Disease; Disease Models, Animal; Embryonic Development - genetics; Embryonic Stem Cells - cytology; Expansion; Genetic aspects; Genetic Diseases, X-Linked; Genetics; Health aspects; Humans; Hypopituitarism; Hypopituitarism - genetics; Hypopituitarism - pathology; Mice; Microscopy; Molecular weight; Mutagenesis; Mutant Proteins - genetics; Mutant Proteins - metabolism; Mutation; Pathology; Peptides - genetics; Peptides - metabolism; Physiological aspects; Physiology, Pathological; Plasmids; Proteins; Proteostasis Deficiencies - genetics; Proteostasis Deficiencies - metabolism; Rodents; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Transcription factors; Australia

Polyalanine expansions in transcription factors have been associated with eight distinct congenital human diseases. It is thought that in each case the polyalanine expansion causes misfolding of the protein that abrogates protein function. Misfolded proteins form aggregates when expressed in vitro;...