Defects in lens fiber differentiation are linked to c-mos overexpression in transgenic mice.
We describe three strains of transgenic mice derived by embryo microinjection of DNA consisting of a long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MSV) linked to the murine c-mos coding sequences. Southern analysis of the genomic DNA of these strains suggested that in each case the transgene had integrated at a different chromosomal location. The strains were characterized by dominant changes in secondary lens fiber differentiation. Shortly after birth, insufficient elongation of differentiating lens fibers and lack of basement membrane secretion resulted in breakdown of the posterior lens capsule. This, in turn led to posterior protrusion and swelling of lens tissue. In the course of the first 3 weeks after birth, globular lens cells began to fill the entire anterior and posterior chambers of the eye. Concomitantly, there was massive overexpression of c-mos RNA in the lens. Whereas this construct has high transforming activity when transfected into NIH-3T3 cells, no hyperplasia or neoplasia have been observed in the affected lenses. Increased expression of c-mos RNA was not confined to the lens of the eye but has been detected in any of several tissues tested.
Khillan
J S
JS
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Oskarsson
M K
MK
Propst
F
F
Kuwabara
T
T
Vande Woude
G F
GF
Westphal
H
H
D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D005838:Genotype; D007908:Lens, Crystalline / Q000196:embryology* / Q000254:growth & development / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008980:Moloney murine sarcoma virus; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger