Investigation of TXNIP (thioredoxin-interacting protein) and TRX (thioredoxin) genes for growth-related traits in pigs Mei Yu, 1,2 Becky Geiger, 3 Nader Deeb, 3 Max F. Rothschild 1 1 Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University, 2255 Kildee Hall, Ames Iowa, 50011, USA 2 Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, PeopleÕs Republic of China 3 PIC/Genus plc, 100 Bluegrass Commons Blvd., Suite 2200, Hendersonville, Tennessee 37075, USA Received: 20 November 2006 / Accepted: 22 January 2007 Abstract It is well known that TRX and its endogenous inhibitor TXNIP help sustain the cellular reduction/ oxidation balance in response to various stresses and both play a crucial role in cell proliferation and growth. Five SNPs were found in TXNIP and these allowed us to map it by linkage to SSC4. Three of the SNPs were used for association analyses in three commercial pig populations (Duroc, Hampshire, and synthetic line) with more than 1200 animals. Both the single-marker and haplotype analyses revealed significant effects of TXNIP on hot carcass weight, test daily gain, and lifetime daily gain. TRX was mapped on SSC1 but no significant associations with growth-related traits were found in the synthetic pig line in which the SNP was informative. The expression levels of TXNIP and TRX were then de- tected in two groups (fast growth and slow growth, respectively) with different genetic backgrounds for growth. Compared with the slow-growth group, TXNIP expression was significantly lower in the fast-growth group, whereas a marked increase in TRX expression was observed in fast-growth group. Our findings suggest that TXNIP has effects on growth-related traits in pigs and further investiga- tions will be necessary to elucidate the underlying mechanisms involved. Introduction Thioredoxin-interacting protein (TXNIP) gene, also termed vitamin D 3 up-regulated protein 1 (VDUP1) or thioredoxin-binding protein-2 (TBP-2) gene, was originally found to be upregulated in HL-60 leuke- mia cells treated with 1,25-dihydroxyvitamin D 3 (Chen and DeLuca 1994). Txnip has been mapped to mouse chromosome 3 band F2.2 (Ludwig et al. 2001), while its human homolog is located on chromosome 1q21, a region that is frequently mu- tated or lost in cases of human cancers (Bieche et al. 1995; Medvedev et al. 1997; Keung et al. 1998). TXNIP is located in the cytoplasm and is a multifunctional protein involved in suppression of cell proliferation and growth and in apoptosis in response to oxidative stress. The role of TXNIP in cell proliferation and growth was mainly evident from the observations that TXNIP inhibits prolif- eration in a variety of cells and exhibits a tumor- suppressive effect in several types of cancer by arresting cells at the G0/G1 phase (Yang et al. 1998; Ikarashi et al. 2002; Schulze et al. 2002; Filby et al. 2006). In alignment with these findings, the expression of TXNIP has been found to be induced dramatically by various stresses or stimuli such as H 2 O 2 , glucose toxicity, anticancer and antiprolifer- ative agents, which in turn renders cells more vulnerable to oxidative stress and could lead to induction of growth arrest and/or apoptosis (Junn et al. 2000; Takahashi et al. 2002; Wang et al. 2002; Minn et al. 2005). To date, one of the currently known mecha- nisms underlying the effects of TXNIP is mediated by inhibition of the reducing activity of thioredoxin (TRX) through direct interaction with the catalytic Correspondence to: Max F. Rothschild; E-mail: mfrothsc@ iastate.edu DOI: 10.1007/s00335-007-9006-8  Volume 18, 197209 (2007)  Ó Springer Science+Business Media, LLC 2007 197