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Drug Metabolism and Disposition Fast Forward
First published on February 26, 2007; DOI: 10.1124/dmd.106.014282


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Dharamainder Choudhary
Ingela Jansson
Karim Rezaul
David K.M. Han
Mansoor Sarfarazi
John B Schenkman
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Received for publication December 12, 2006.
Revised February 23, 2007.
Accepted for publication February 23, 2007.

Cyp1b1 protein in the mouse eye during development: An immunohistochemical study

Dharamainder Choudhary 1, Ingela Jansson 1, Karim Rezaul 1, David K.M. Han 1, Mansoor Sarfarazi 1, John B Schenkman 1*

1 University of Connecticut

* Address correspondence to: E-mail: jschenkm{at}neuron.uchc.edu

Abstract

We show, for the first time, the spatio-temporal appearance of Cyp1b1 protein during mouse eye ontogeny. The protein was unambiguously identified in the adult mouse eye and newborn (P0) whole mouse microsomes, and shown to be localized in inner ciliary epithelium, corneal epithelium, retinal inner nuclear cells and ganglion cells. The enzyme protein was present in the lens epithelium adjacent to the developing ciliary body at 15.5 days post conception (E15.5) and was most strongly expressed during E17.5 - P07. Subsequently, it declined to very low levels. The protein was also expressed in the corneal endothelial cells adjacent to the ciliary body at 7 days postnatally (P07). Cyp1b1 was barely detectable in the inner ciliary epithelium before E17.5 but increased rapidly postnatally, reaching adult levels by P28. Levels of the enzyme protein in the corneal epithelium were seen from E15.5 onward, rising sharply, and after a decline at P07, was highest in the adult animal eye. The presence of Cyp1b1 protein in the inner nuclear layer of the retina was very low in the prenatal eye, rising rapidly postnatally, and was highest in the adult animal eye. In the ganglion cell layer of the retina it increased slowly from E15.5 to P07, and then rapidly reached adult levels. Interestingly, Cyp1b1 was not detected in the trabecular meshwork at any stage of development or in the adult eye. We conclude that the enzyme may play important roles in the normal eye development and function in mouse as in human, and that the mouse may prove to be an excellent model for determination of the roles of CYP1B1 in human eye development and function.


Key words: CYP expression, CYP1B, cytochrome P450 function, extrahepatic cytochrome P450





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