Lens expression of TGF alpha in transgenic mice produces two distinct eye pathologies in the absence of tumors

Oncogene. 1994 Jul;9(7):1965-75.

Abstract

Transgenic mice carrying the rat TGF alpha minigene linked to the alpha A crystallin promoter were generated to investigate the effects of expression of this growth factor in the lens of the eye. All transgenic mice exhibited eye abnormalities in the absence of overt tumors, and two distinct and heritable phenotypes were observed. Five lineages produced 'squinting' transgenic mice characterized by microphthalmic eyes with severe lens and retinal dysplasia, and four lineages produced 'bulged' transgenic mice with eyes that exhibited enlarged globes, lens epithelial hyperplasia, anterior segment dysgenesis, and in some cases retinal dysplasia. The eye perturbations of both phenotypes were evident histologically by 1 week of age, and the eyes of squinting mice were abnormal during embryonic development. The squinting phenotype was dominant over the bulged phenotype in intercrosses, suggesting that position effects from the transgene integration site resulted in differences in TGF alpha expression between the two phenotypes. In situ hybridization showed that TGF alpha transgene expression was confined to the lens or lens rudiment of all transgenic eyes despite the involvement of non-lenticular tissues in the pathology. These results show that inappropriate expression of TGF alpha in the eye can disrupt the communication required to coordinate normal eye development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Eye Abnormalities / etiology*
  • Eye Abnormalities / genetics
  • Eye Abnormalities / pathology
  • Eye Neoplasms / genetics
  • Female
  • In Situ Hybridization
  • Lens, Crystalline / embryology
  • Lens, Crystalline / metabolism*
  • Lens, Crystalline / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Pedigree
  • Phenotype
  • Transforming Growth Factor alpha / biosynthesis
  • Transforming Growth Factor alpha / genetics
  • Transforming Growth Factor alpha / physiology*

Substances

  • Transforming Growth Factor alpha