title: Do Genetic Alterations in Sex Steroid Receptors Contribute to Lacrimal Gland Disease in Sjögren's Syndrome?
abstract: BACKGROUND: Defects in sex steroid receptors have been linked to the onset, progression and severity, as well as the sex-related prevalence, of a variety of autoimmune disorders, including lupus, rheumatoid arthritis, multiple sclerosis and diabetes. We hypothesize that defects in estrogen receptor alpha (ESR1), estrogen receptor beta (ESR2) and/or the androgen receptor (AR) may also contribute to the development of lacrimal gland autoimmune sequelae in Sjögren's syndrome. To begin to test this hypothesis, we examined whether mutations exist in the coding regions of ESR1, ESR2 and AR transcripts in lacrimal tissues of mouse models of Sjögren's syndrome. METHODS: Lacrimal and submandibular glands were collected from adult MRL/MpJ-Tnfrsf6(lpr), nonobese diabetic and/or BALB/c mice. Tissues were pooled according to sex and experiment and processed for cDNA generation. PCR primers were designed to amplify 566-875 base pair segments of the entire open reading frame of each receptor. Segments were amplified, purified and then sequenced. Receptor sequences were assembled and compared to each other and to known NCBI sequences. RESULTS: Our results show that almost all ESR1, ESR2 and AR sequences in exocrine tissues of male and female autoimmune and non-autoimmune mice were identical to those of NCBI standards. There was a G-->A shift at position 998 of the ESR2 complete coding sequence in all tissue samples when compared to NCBI reference sequence U81451.1, but this polymorphism was not found in other ESR2 reference sequences. CONCLUSIONS: Our findings indicate that defects in the coding region of sex steroid receptors do not contribute to the pathogenesis of lacrimal gland disease in mouse models of Sjögren's syndrome.
authors.affiliation: Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Richards
authors.forename: David A
authors.initials: DA
authors.lastname: Sullivan