Premium
Molecular misreading in non‐neuronal cells
Author(s) -
Van Leeuwen Fred W.,
Hol Elly M.,
Hermanussen Rob W. H.,
Sonnemans Marc A. F.,
Moraal Ewoud,
Fischer David F.,
Evans Dana A. P.,
Chooi KUMFAI,
Burbach J. Peter H.,
Murphy David
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.99-0825com
Subject(s) - biology , microbiology and biotechnology , minigene , genetically modified mouse , gene , transgene , messenger rna , alternative splicing , genetics
+1 Frame‐shifted proteins such as amyloid precursor protein+ 1 and ubiquitin‐B +1 have been identified in the neuropathological hallmarks of Alzheimer's disease. These frameshifts are caused by dinucleotide deletions in GAGAG motifs of mes· senger RNA encoded by genes that have maintained the unchanged wild‐type DNA sequence. This process is termed ‘molecular misreading’. A key question is whether this process is confined to neurons or whether it could also occur in non‐neuronal cells. A transgenic mouse line (MV‐B) carrying multiple copies of a rat vasopressin minigene as a reporter driven by the MMTV‐LTR promotor was used to screen non‐neuronal tissues for molecular misreading by means of detection of the rat vasopressin+ 1 protein and mutated mRNA. Molecular misreading was demonstrated to occur in several organs (e.g., epididymis and the parotid gland) where transgenic vasopressin expression is abundant, but its penetrance is variable both between and within tissues. This implies that non‐neural tissues too, could be affected by cellular derangements caused by molecular misreading.–van Leeuwen, F. W., Hol, E. M., Hermanussen, R. W. H., Sonnemans, M. A. F., Moraal, E., Fischer, D. F., Evans, D. A. P., Chooi, K.‐F., Burbach, J. P. H., Murphy, D. Molecular misreading in non‐neuronal cells. FASEB J. 14, 1595–1602 (2000)