Expression of Usherin in Human Tissues: Implications for Diagnostics and Pathology

Usher Syndrome is an autosomal recessive disease that results in varying degrees of hearing loss and retinitis pigmentosa. Three types of Usher Syndrome (1,11, and III) have been identified clinically with Usher type II being the most common. Usher type !! has been localized to three different chromosomes lq41, 3p, and 5q, corresponding to Usher type 2A, 2B, and 2C respectively. Usherin is a basement membrane protein encoded by the USH2A gene. Expression of usherin has been localized in the basement membrane of several tissues, however it is not ubiquitous. Understanding localization of usherin is a key first step in defining its function in vivo. These studies aimed to define the pattern of usherin expression in human tissues. Immunohistochemistry detected usherin in the following human tissues: retina, cochlea, small and large intestine, pancreas, bladder, prostate, esophagus, trachea, thymus, salivary glands, placenta, ovary, fallopian tube, uterus, and testis. Usherin was absent in many other tissues such as heart, lung, liver, kidney, and brain. This distribution is consistent with the usherin distribution in the mouse. Conservation of usherin is also present at the nucleotide and amino acid level when comparing the mouse and human gene and protein sequences. Evolutionary conservation of usherin expression at the molecular level and in tissues unaffected in USH2A supports the important structural and functional role this protein plays in the human. RNA was analyzed from patients who were affected with Usher 2a or carried an USH2A mutation. RNA did not amplify from the patient with Usher 2a and the carrier of an USH2A mutation had approximately half as much USH2A RNA as controls. These results, in conjunction with immunodetection of usherin, could lead to diagnostic procedures for th& detection of Usher Syndrome Type 11a and carriers of an USH2A alleie. The presence of usherin in the reproductive tissues prompted the investigation of reproductive patterns among those with Usher 11a. Evaluation of pregnancy and birth rates of those with Usher 11a demonstrates no statistical difference from those not affected with Usher 11a. Although normal usherin expression is essential for proper development and function of both the inner ear and retina, it does not seem necessary for reproduction in people with Usher 11a. Nevertheless, evolutionary conservation of expression in tissues unaffected in USH2A raises interesting issues regarding the source of evolutionary pressures.

Grantor dc:publisher

Creighton University

Year dc:date.issued

2002

Author dc:creator

• Pearsall, Nicole

Advisor dc:contributor.advisor

• Kimberling, William J.

Statement dc:rights

• Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10504/68458

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/68458