The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts.
OBJECTIVE
To sequence and comprehensively analyze human and mouse lacrimal gland transcriptomes as part of the NEIBank project.


METHODS
cDNA libraries generated from normal human and mouse lacrimal glands were sequenced and analyzed by PHRED, RepeatMasker, BLAST, and GRIST. Human "lacrimal-preferred genes" and putative gene regulatory elements were respectively identified in UniGene and ConSite, and gene clustering was analyzed by chromosomal mapping. "Hypothetical proteins," identified by keyword search, were verified by genomic alignment and queried in the Conserved Domain database and GEO Profiles.


RESULTS
The top six transcripts in human and mouse differed, revealing a previously unappreciated molecular divergence. The human transcriptome is enriched with transcripts from 29 lacrimal-preferred genes and a content of poorly characterized hypothetical proteins, proportionally greater than in all other tissues. Only 45% of lacrimal preferred, but 71% of hypotheticals, have mouse orthologs. Many of the latter display apparently altered cancer expression in the CGAP SAGE library collection-often in keeping with predicted WD40, protein kinase, Src homology 2 and 3, RhoGEF, and pleckstrin homology domains involved in cell signaling. At the genomic level, lacrimal-expressed genes show some evidence of clustering, particularly on human chromosomes 9 and 12. Binding sites for TFAP2A, FOXC1, and other transcription factors are predicted.


CONCLUSIONS
Interspecies divergence cautions against use of mouse models of human dry eye syndromes. Lacrimal preferred and hypothetical proteins, gene clustering, and putative gene regulatory elements together provide new clues for a molecular understanding of lacrimal gland function and mechanisms of coordinated tissue-specific transcriptional regulation.
Ozyildirim
Aylin M
AM
Department of Cell Biology, UVa Health System, University of Virginia, Charlottesville, VA 22908 USA.
Wistow
Graeme J
GJ
Gao
James
J
Wang
Jiahu
J
Dickinson
Douglas P
DP
Frierson
Henry F
HF
Laurie
Gordon W
GW
D000368:Aged; D000818:Animals; D019295:Computational Biology; D020224:Expressed Sequence Tags; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007765:Lacrimal Apparatus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016324:Sequence Tagged Sites; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology*
D014157:Transcription Factors