Development of cataracts in a line of mice transgenic for human rhodopsin-promoted LacZ

Academic Article

Abstract

  • Purpose: To characterize the histopathologic and genetic basis of cataract formation in the transgenic line of mice, Tg-1576HRP/acZ-9. Mice of this line contain the bacterial lacZ gene driven by the 1.58 kb sequence immediately upstream to the human rhodopsin gene. Methods: Transgenic mice generated after microinjection into nuclei of fertilized B6SJLF1/J eggs were bred with either B6 or CD-1 mice and identified by Southern blot analysis or PCR amplification of the transgene. Transgenic mouse eyes were examined by indirect ophmalmoscopy and then histologically in paraffin sections from birth through 6 months of age, LacZ expression was assessed immunohistochemically and by in situ hybridization. LacZ expression patterns were also assessed with Western analysis. Results: Cataracts in transgenic mice were first apparent clinically as spoke-like changes and histologically as vacuolar posterior subcapsular abnormalities starting 4 weeks after birth. By 4 months after birth, cataracts were mature and often ruptured through the posterior capsule. At this age, mice possessed a tremor and hunched posture. No gross abnormalities were detected, however, in the brain or other ocular structures. Immunohistochemistry and Western blot analyses revealed lacZ expression limited to photoreceptors and weaker expression in non-pigmented ciliary epithelium beginning -postnatal day 11. LacZ expression was not detected in the lens. Cataracts were inherited in an autosomal recessive fashion. In contrast, the transgene was inherited in a dominant fashion. A separate line of mice carrying the same transgene had a similar pattern of transgene expression and inheritance but no cataracts. Conclusions: Cataract formation in this line of transgenic mice appears to be unrelated to inheritance of the transgene. This phenotype has not been reported previously. This studv describes a new animal mndfl fnr «mrivino the deve.lonmeni and Ireatment of autnsomal recessive cataracts.
  • Authors

    Author List

  • Bajwa R; Klatt L; Kapadia M; Zeng Y; Bennett J
  • Volume

  • 38
  • Issue

  • 4