Xiphophorus fishes have been used as a vertebrate experimental model for fundamental biomedical research for over 60 years. This R24 proposal outlines both resource and research components designed to maintain and enhance the Xiphophorus Genetic Stock Center (XGSC) that has operated within the United States since the 1930's making it one of the oldest live animal resources centers worldwide and a national scientific treasure. The XGSC houses over 60 pedigreed genetic lines representing 25 Xiphophorus species in over 1,400 aquaria. The XGSC has provided pedigreed fish and materials to researchers in over 30 laboratories representing 11 countries. The traditional strength of the Xiphophorus experimental model involves the non-biased assessment of genetic inheritance patterns associated with complex phenotypes within intact animals. For example, genetic control of tumor susceptibility has been documented in both pure Xiphophorus strains and select interspecies hybrids, for a variety of spontaneous and induced neoplasms including several genetically distinct melanomas. Our preliminary studies represent a first global comparison of the relative abundance of species-specific allele expression in two vertebrate species and Fl hybrids. In this initial study we were able to identify substantial changes in gene expression levels for parental alleles in the interspecies hybrid genetic background. We also found a new class of genetic interactions that lead to substantially suppressed gene expression in Fl hybrids relative to either parent. These initial experiments, employing RNAseq to follow allele specific gene expression in Fl interspecies hybrids, serve as examples of the Xiphophorus model may be used to uncover new knowledge regarding the mechanics of gene interactions, the genetic basis of developmental programs, complex behaviors, and the molecular processes underlying disease initiation and progression. If the goals of this proposal are realized, mechanistic dissection of Xiphophorus interspecies hybrid melanoma models may be approached and the results gleaned will have translational significance to tumorigenesis in humans.

Public Health Relevance

If the goals of this proposal are realized, mechanistic dissection of Xiphophorus interspecies hybrid melanoma models may be approached since genome and transcriptome sequences of both parental species will allow assessment of genetic regulatory changes that produce an individual that is predisposed to melanoma. These results will have direct translational significance to tumorigenesis in humans.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
5R24OD011120-06
Application #
8467078
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Chang, Michael
Project Start
2008-04-01
Project End
2016-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
6
Fiscal Year
2013
Total Cost
$689,125
Indirect Cost
$180,893
Name
Texas State University-San Marcos
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
074602368
City
San Marcos
State
TX
Country
United States
Zip Code
78666
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Lu, Yuan; Boswell, Mikki; Boswell, William et al. (2018) Comparison of Xiphophorus and human melanoma transcriptomes reveals conserved pathway interactions. Pigment Cell Melanoma Res 31:496-508
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