Advertisement

Transgenic Research

, Volume 23, Issue 2, pp 341–349 | Cite as

A promoter that drives gene expression preferentially in male transgenic rats

  • Qiling Li
  • Yamin Ma
  • Wenzhi Li
  • Wei Xu
  • Li Ma
  • Guoxing Fu
  • Xiaohua Tian
  • Yueling Wang
  • Xu Li
  • Tameka Bythwood
  • Jendai Richards
  • Mukaila A. Akinbami
  • Qing SongEmail author
Original Paper

Abstract

Gender-preferential gene expression is a widespread phenomenon in humans. It is important to study how gender differences influence the pathogenesis of various diseases and response to specific drugs. The aim of this study is to determine if the mouse albumin enhancer/promoter may serve as the promoter to introduce gender-preferential gene expression in transgenic animals. We created four independent transgenic rat lines in which the human C-reactive protein transgene was under the control of mouse albumin enhancer/promoter. Quantitative real time RT-PCR analysis showed that transgene expression in the liver of male rats was significantly higher than transgene expression in the female rats (P < 0.05).There was a 5.3-fold (male/female) difference in line-519, and a 12.2-fold (male/female) difference in line-488. Enzyme-linked immunosorbent assay showed that the serum of male transgenic rats had a 13- to 679-fold difference at the protein level on transgene production compared with female transgenic rats. The male-to-female difference in gene expression was 10- to 17-fold in the liver of transgenic rats. Orchiectomy dramatically reduced protein production from the transgene in the liver. Testosterone administration into female rats did not increase the transgene expression, but estrogen administration into the male rats reduced transgene expression. This study provides a valuable tool for investigating the pathological roles of genes that are expressed in a gender-preferential manner in human disease.

Keywords

Gender-preferential Transgenic Animal model Gene expression 

Notes

Acknowledgments

This work was supported by NIH Grants (HG006173, MD005964, HL095098, RR003034), American Heart Association Grant (09GRNT2300003). We acknowledge Wanda Filipiak for preparation of transgenic rats and the Transgenic Animal Model Core of the University of Michigan’s Biomedical Research Core Facilities.

Conflict of interest

The authors have declared that no competing interests exist.

References

  1. Clark AJ, Bissinger P, Bullock DW, Damak S, Wallace R, Whitelaw CB, Yull F (1994) Chromosomal position effects and the modulation of transgene expression. Reprod Fertil Dev 6(5):589–598PubMedCrossRefGoogle Scholar
  2. Filipiak WE, Saunders TL (2006) Advances in transgenic rat production. Transgenic Res 15(6):673–686PubMedCrossRefGoogle Scholar
  3. Heidecker B, Lamirault G, Kasper EK, Wittstein IS, Champion HC, Breton E, Russell SD, Hall J, Kittleson MM, Baughman KL, Hare JM (2010) The gene expression profile of patients with new-onset heart failure reveals important gender-preferential differences. Eur Heart J 31(10):1188–1196PubMedCentralPubMedCrossRefGoogle Scholar
  4. Kimoto H, Haga S, Sato K, Touhara K (2005) Sex-specific peptides from exocrine glands stimulate mouse vomeronasal sensory neurons. Nature 437(7060):898–901PubMedCrossRefGoogle Scholar
  5. Palmiter RD, Brinster RL (1986) Germ-line transformation of mice. Annu Rev Genet 20:465–499PubMedCrossRefGoogle Scholar
  6. Pfeifer C, Aneja MK, Hasenpusch G, Rudolph C (2011) Adeno-associated virus serotype 9-mediated pulmonary transgene expression: effect of mouse strain, animal gender and lung inflammation. Gene Ther 18(11):1034–1042PubMedCrossRefGoogle Scholar
  7. Si H, Banga RS, Kapitsinou P, Ramaiah M, Lawrence J, Kambhampati G, Gruenwald A, Bottinger E, Glicklich D, Tellis V, Greenstein S, Thomas DB, Pullman J, Fazzari M, Susztak K (2009) Human and murine kidneys show gender- and species-specific gene expression differences in response to injury. PLoS One 4(3):e4802PubMedCentralPubMedCrossRefGoogle Scholar
  8. Simunovic F, Yi M, Wang Y, Stephens R, Sonntag KC (2010) Evidence for gender-preferential transcriptional profiles of nigral dopamine neurons in Parkinson disease. PLoS One 5(1):e8856PubMedCentralPubMedCrossRefGoogle Scholar
  9. Sugamori KS, Brenneman D, Grant DM (2011) Liver-selective expression of human arylamine N-acetyltransferase NAT2 in transgenic mice. Drug Metab Dispos 39(5):882–890PubMedCrossRefGoogle Scholar
  10. Vawter MP, Evans S, Choudary P, Tomita H, Meador-Woodruff J, Molnar M, Li J, Lopez JF, Myers R, Cox D, Watson SJ, Akil H, Jones EG, Bunney WE (2004) Gender-preferential gene expression in post-mortem human brain: localization to sex chromosomes. Neuropsychopharmacology 29(2):373–384PubMedCentralPubMedCrossRefGoogle Scholar
  11. Zhang W, Bleibel WK, Roe CA, Cox NJ, Eileen Dolan M (2007) Gender-preferential differences in expression in human lymphoblastoid cell lines. Pharmacogenet Genomics 17(6):447–450PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Qiling Li
    • 1
    • 2
  • Yamin Ma
    • 2
  • Wenzhi Li
    • 2
  • Wei Xu
    • 2
  • Li Ma
    • 2
  • Guoxing Fu
    • 2
  • Xiaohua Tian
    • 2
  • Yueling Wang
    • 1
  • Xu Li
    • 1
  • Tameka Bythwood
    • 2
  • Jendai Richards
    • 2
  • Mukaila A. Akinbami
    • 2
  • Qing Song
    • 1
    • 2
    Email author
  1. 1.Department of Obstetrics and Gynecology, First Affiliated HospitalXi’an Jiaotong UniversityXi’anChina
  2. 2.Cardiovascular Research InstituteMorehouse School of MedicineAtlantaUSA

Personalised recommendations