Neuropathological changes in transgenic mice carrying copies of a transcriptionally activated Mos protooncogene.
Independent transgenic mouse lines carrying the mouse Mos protooncogene linked to a retroviral transcriptional control sequence display behavioral abnormalities including circling, head tilting, and head bobbing. This dominant phenotype shows various degrees of penetrance in different transgenic founder animals and lines. Neuronal and axonal degeneration, gliosis, and inflammatory infiltrates are found in all transgenic mouse lines in which behavioral traits are present. Recordings of auditory-evoked potentials in mice of one of these lines demonstrate that transgenic mice are deaf; in these mice spiral ganglia degenerate and most of the cochlear hair cells are absent. By using an S1 nuclease protection assay, we have detected RNA expression of the transgene in all tissues examined and, in particular, at high levels in brain. In situ hybridization experiments show that Mos expression can be detected in specific areas of the central nervous system. Lesions are present in areas with demonstrable overexpression of Mos.
Propst
F
F
ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.
Rosenberg
M P
MP
Cork
L C
LC
Kovatch
R M
RM
Rauch
S
S
Westphal
H
H
Khillan
J
J
Schulz
N T
NT
Vande Woude
G F
GF
Neumann
P E
PE
Newmann
P E
PE
D000818:Animals; D001921:Brain / Q000473:pathology*; D005260:Female; D006198:Hair Cells, Auditory / Q000473:pathology; D007249:Inflammation; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017231:Proto-Oncogene Proteins c-mos; D011519:Proto-Oncogenes; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic
D011518:Proto-Oncogene Proteins; D012313:RNA; D011505:Protein-Tyrosine Kinases; D017231:Proto-Oncogene Proteins c-mos