Expression patterns of cytochrome P4501B1 (Cyp1b1) in FVB/N mouse eyes

Exp Eye Res. 2002 Sep;75(3):249-57.

Abstract

Homozygous and compound heterozygous mutations in cytochrome P4501B1 (CYP1B1) cause primary congenital glaucoma (PCG) in humans. It is hypothesized that developmental anomalies of the trabecular meshwork prevent appropriate drainage of the aqueous humor and cause PCG in human patients. In this report, we studied the expression patterns of Cyp1b1 in the eye of albino FVB/N mouse at different developmental stages. We isolated a cDNA fragment corresponding to the 3'untranslated region (3'UTR) of the Cyp1b1 gene by PCR and used it to make an (35)S-labelled riboprobe for in situ hybridization. We found that Cyp1b1 is expressed in both anterior and posterior segments of the eye. Anteriorly, the expression is confined to the ciliary body, most likely in the outer/pigmented ciliary epithelial cells. Cyp1b1 mRNA can be detected in these cells at postnatal day 4 (P4) and the expression continues into adulthood. Surprisingly, no above-background levels of Cyp1b1 mRNA were found at or around the trabecular meshwork at all the stages we examined. In the posterior region of the embryonic day 15 (E15) eye, Cyp1b1 is expressed in the retinal neuroepithelium and in the tissues surrounding the optic nerve, but not in the optic nerve itself. In the P7 retina, Cyp1b1 mRNA is found in the inner nuclear layer. Based on our finding that Cyp1b1 is expressed in the developing and mature ciliary body of the mouse eye, we speculate that mutation in this gene can directly contribute to the abnormal elevation of the intraocular pressure (IOP) in the PCG patients or indirectly affect the aqueous outflow by disrupting the proper development of the trabecular meshwork in these patients.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Aqueous Humor / metabolism
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Ciliary Body / metabolism
  • Cytochrome P-450 CYP1B1
  • DNA, Complementary / genetics
  • Eye / embryology*
  • Eye / enzymology*
  • Gene Expression Regulation, Developmental*
  • Glaucoma / congenital*
  • Glaucoma / embryology
  • In Situ Hybridization
  • Mice
  • Mice, Inbred Strains
  • RNA, Messenger / genetics
  • Trabecular Meshwork / metabolism

Substances

  • 3' Untranslated Regions
  • DNA, Complementary
  • RNA, Messenger
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cyp1b1 protein, mouse
  • Cytochrome P-450 CYP1B1