Related Experiment Videos
Defects in lens fiber differentiation are linked to c-mos overexpression in transgenic mice
J S Khillan1, M K Oskarsson, F Propst
1Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Abstract:
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.
Insights
Transgenic mice with Moloney murine sarcoma virus LTR linked to c-mos developed severe eye abnormalities due to c-mos overexpression. Despite high transforming activity in cell lines, no tumors formed in the affected mouse lenses.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- The c-mos proto-oncogene plays a critical role in cellular regulation.
- Understanding the in vivo effects of c-mos overexpression is essential for developmental biology.
Purpose of the Study:
- To investigate the effects of introducing a c-mos transgene into mice.
- To analyze the consequences of c-mos overexpression on lens development and tumor formation.
Main Methods:
- Generation of three transgenic mouse strains via embryo microinjection of a DNA construct containing the Moloney murine sarcoma virus LTR linked to murine c-mos.
- Southern analysis of genomic DNA to determine transgene integration sites.
- Histological examination of ocular tissues and RNA expression analysis.
Main Results:
- Transgenic mice exhibited dominant changes in secondary lens fiber differentiation, leading to lens capsule breakdown and posterior protrusion.
- Lens cells filled anterior and posterior chambers, with massive c-mos RNA overexpression specifically in the lens.
- Despite the construct's transforming activity in NIH-3T3 cells, no hyperplasia or neoplasia were observed in the affected lenses.
Conclusions:
- Overexpression of c-mos in the lens disrupts normal differentiation and leads to severe ocular abnormalities without inducing cancer.
- The cellular environment of the lens may resist oncogenic transformation mediated by c-mos.