Skip to main content
SpringerLink
Log in

Genetic Relatedness of WNIN and WNIN/Ob with Major Rat Strains in Biomedical Research

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

WNIN (Wistar/NIN) is an inbred rat strain maintained at National Institute of Nutrition (NIN) for more than 90 years, and WNIN/Ob is an obese mutant originated from it. To determine their genetic relatedness with major rat strains in biomedical research, they were genotyped at various marker loci. The recently identified markers for albino and hooded mutations which clustered all the known albino rats into a single lineage also included WNIN and WNIN/Ob rats. Genotyping using microsatellite DNA markers and phylogenetic analysis with 49 different rat strains suggested that WNIN shares a common ancestor with many Wistar originated strains. Fst estimates and Fischer’s exact test suggest that WNIN rats differed significantly from all other strains tested. WNIN/Ob though shows hyper-leptinemia, like Zucker fatty rat, did not share the Zucker fatty rat mutation. The above analyses suggest WNIN as a highly differentiated rat strain and WNIN/Ob a novel obese mutant evolved from it.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aitman TJ, Critser JK, Cuppen E, Dominiczak A, Fernandez-Suarez XM, Flint J, Gauguier D, Geurts AM, Gould M, Harris PC, Holmdahl R, Hubner N, Izsvák Z, Jacob HJ, Kuramoto T, Kwitek AE, Marrone A, Mashimo T, Moreno C, Mullins J, Mullins L, Olsson T, Pravenec M, Riley L, Saar K, Serikawa T, Shull JD, Szpirer C, Twigger SN, Voigt B, Worley K (2008) Progress and prospects in rat genetics: a community view. Nat Genet 40(5):516–522

    Article  CAS  PubMed  Google Scholar 

  • Albuquerque D, Stice E, Rodríguez-López R, Manco L, Nóbrega C (2015) Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective. Mol Genet Genomics. Mar 8. [Epub ahead of print] PubMed PMID:25749980

  • Atanur SS, Diaz AG, Maratou K, Sarkis A, Rotival M, Game L, Tschannen MR, Kaisaki PJ, Otto GW, Ma MC, Keane TM, Hummel O, Saar K, Chen W, Guryev V, Gopalakrishnan K, Garrett MR, Joe B, Citterio L, Bianchi G, McBride M, Dominiczak A, Adams DJ, Serikawa T, Flicek P, Cuppen E, Hubner N, Petretto E, Gauguier D, Kwitek A, Jacob H, Aitman TJ (2013) Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat. Cell 154(3):691–703

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bandaru P, Rajkumar H, Nappanveettil G (2011) Altered or impaired immune response upon vaccination in WNIN/Ob rats. Vaccine 29:3038–3042

    Article  CAS  PubMed  Google Scholar 

  • Beermann F, Orlow SJ, Lamoreux ML (2004) The Tyr (albino) locus of the laboratory mouse. Mamm Genome 15:749–758

    Article  CAS  PubMed  Google Scholar 

  • Canzian F (1997) Phylogenetics of the laboratory rat Rattus norvegicus. Genome Res 7:262–267

    Article  CAS  PubMed  Google Scholar 

  • Dwinell MR, Lazar J, Geurts AM (2011) The emerging role for rat models in gene discovery. Mamm Genome 22:466–475

    Article  PubMed Central  PubMed  Google Scholar 

  • Felsenstein J (2009) PHYLIP (Phylogeny Inference Package) version 3.69 Distributed by the author. Department of Genome Sciences, University of Washington. http://evolution.genetics.washington.edu/phylip.html. Accessed 23 July 2014

  • Festing MFW (1993) International Index of Laboratory Animals, 6th edn. University of Leicester, Leicester, p 186

    Google Scholar 

  • Ginter E, Simko V (2014) Becoming overweight: is there a health risk? Bratisl Lek Listy 115(9):527–531

    CAS  PubMed  Google Scholar 

  • Giridharan NV (1998) Animal models of obesity & their usefulness in molecular approach to obesity. Indian J Med Res 108:225–242

    CAS  PubMed  Google Scholar 

  • Giridharan N, Harishankar N, Satyavani M (1996) A new rat model for the study of Obesity. Scand J Lab Anim Sci 23:131–137

    Google Scholar 

  • Harishankar N, Kumar PU, Sesikeran B, Giridharan N (2011a) Obesity associated pathophysiological & histological changes in WNIN obese mutant rats. Indian J Med Res 134:330–340

    PubMed Central  PubMed  Google Scholar 

  • Harishankar N, Ravinder P, Nair KM, Giridharan N (2011b) Infertility in WNIN Obese Mutant Rats-Causes? ISRN Endocrinol 2011:863403

    Article  PubMed Central  PubMed  Google Scholar 

  • Kalashikam RR, Battula KK, Kirlampalli V, Friedman JM, Nappanveettil G (2013) Obese locus in WNIN/obese rat maps on chromosome 5 upstream of leptin receptor. PLoS ONE 81:e77679

    Article  Google Scholar 

  • Kalashikam RR, Inagadapa PJ, Thomas AE, Jeyapal S, Giridharan NV, Raghunath M (2014) Leptin gene promoter DNA methylation in WNIN obese mutant rats. Lipids Health Dis 13:25

    Article  PubMed Central  PubMed  Google Scholar 

  • Kiran KB, Vijaya BN, Vishnuvardhan RM, Giridharan N (2007) DNA fingerprinting and phylogenetic analysis of WNIN rat strain and its obese mutants using microsatellite markers. Biochem Genet 45:77–91

    Article  CAS  PubMed  Google Scholar 

  • Kuramoto T, Nakanishi S, Ochiai M, Nakagama H, Voigt B, Serikawa T (2012) Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains. PLoS ONE 7:e43059

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leibel RL, Chung WK, Chua SC Jr (1997) The molecular genetics of rodent single gene obesities. J Biol Chem 272:31937–31940

    Article  CAS  PubMed  Google Scholar 

  • Lifshitz F, Lifshitz JZ (2014) Globesity: the root causes of the obesity epidemic in the USA and now worldwide. Pediatr Endocrinol Rev 12(1):17–34

    PubMed  Google Scholar 

  • Lindesy JR, Baker HJ (2006) Historical Foundations. In: Suckow MA, Steven HW, Craig LF (eds) The laboratory rat, 2nd edn. Elsevier Acadamic Press, Burlington, pp 33–34

    Google Scholar 

  • Lutz TA, Woods SC (2012) Overview of animal models of obesity. Curr Protoc Pharmacol Chapter 5:Unit5.61. doi:10.1002/0471141755.ph0561s58

    PubMed  Google Scholar 

  • Mashimo T, Serikawa T (2009) Rat resources in biomedical research. Curr Pharm Biotechnol 10:214–220

    Article  CAS  PubMed  Google Scholar 

  • Mashimo T, Voigt B, Tsurumi T, Naoi K, Nakanishi S, Yamasaki K, Kuramoto T, Serikawa T (2006) A set of highly informative rat simple sequence length polymorphism (SSLP) markers and genetically defined rat strains. BMC Genet 7:19

    Article  PubMed Central  PubMed  Google Scholar 

  • Miller Mark P (1997) Tools for population genetic analyses (TFPGA) 1.3: a Windows program for the anlaysis of allozyme and molecular population genetic data of rat inbred strains. Mamm Genome 14:61–64

    Google Scholar 

  • Nei M (1978) Estimation of average heterozygosity and genetic distance from a small number of individuals. Genetics 89:583–590

    PubMed Central  CAS  PubMed  Google Scholar 

  • Page RDM (1996) TREEVIEW: an application to display phylogenetic trees on personal computers. Comput Appl Biosci 12:357–358

    CAS  PubMed  Google Scholar 

  • Reddy GB, Vasireddy V, Mandal MN, Tiruvalluru M, Wang XF, Jablonski MM, Nappanveettil G, Ayyagari R (2009) A novel rat model with obesity-associated retinal degeneration. Invest Ophthalmol Vis Sci 50:3456–3463

    Article  PubMed  Google Scholar 

  • Rousset F (2008) Genepop’007: a complete reimplementation of the Genepop software for Windows and Linux. Mol Ecol Resour 8:103–106

    Article  PubMed  Google Scholar 

  • Sáinz N, Barrenetxe J, Moreno-Aliaga MJ, Martínez JA (2015) Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism 64(1):35–46

    Article  PubMed  Google Scholar 

  • Schutz Y, Byrne NM, Dulloo A, Hills AP (2014) Energy gap in the aetiology of body weight gain and obesity: a challenging concept with a complex evaluation and pitfalls. Obes Facts 7(1):15–25

    Article  PubMed  Google Scholar 

  • Serikawa T, Kuramoto T, Hilbert P, Mori M, Yamada J, Dubay CJ, Lindpainter K, Ganten D, Guénet JL, Lathrop GM, Beckman JS (1992) Rat gene mapping using PCR-analyzed microsatellites. Genetics 131(3):701–721

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shimoyama M, De Pons J, Hayman GT, Laulederkind SJ, Liu W, Nigam R, Petri V, Smith JR, Tutaj M, Wang SJ, Worthey E, Dwinell M, Jacob H (2015) The Rat Genome Database 2015: genomic, phenotypic and environmental variations and disease. Nucleic Acids Res 43(Database issue):D743-50

    PubMed  Google Scholar 

  • Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378(9793):804–814

    Article  PubMed  Google Scholar 

  • Szpirer C, Levan G (2012) Rat Genome Mapping and Genomics. In: Denny P, Kole C (eds) Genome Mapping and Genomics in Laboratory Animals, vol 4th. Springer, Berlin, pp 217–256

    Chapter  Google Scholar 

  • Thomas MA, Chen CF, Jensen-Seaman MI, Tonellato PJ, Twigger SN (2003) Phylogenetics of rat inbred strains. Mamm Genome 14:61–64

    Article  PubMed  Google Scholar 

  • Watanabe TK, Bihoreau MT, McCarthy LC, Kiguwa SL, Hishigaki H, Tsuji A, Browne J, Yamasaki Y, Mizoguchi-Miyakita A, Oga K, Ono T, Okuno S, Kanemoto N, Takahashi E, Tomita K, Hayashi H, Adachi M, Webber C, Davis M, Kiel S, Knights C, Smith A, Critcher R, Miller J, Thangarajah T, Day PJ, Hudson JR Jr, Irie Y, Takagi T, Nakamura Y, Good Fellow PN, Lathrop GM, Tanigami A, James MR (1999) A radiation hybrid map of the rat genome containing 5255 markers. Nat Genet 22(1):27–36

    Article  CAS  PubMed  Google Scholar 

  • Wauman J, Tavernier J (2011) Leptin receptor signaling: pathways to leptin resistance. Front Biosci (Landmark edn). 16:2771–2793

Download references

Acknowledgments

Authors acknowledge the Indian Council of Medical Research (ICMR), Government of India, National Institutes of Health (NIH), USA, Rockefeller University, NY, USA, for the research fund. We thank lab members of Dr. Friedman, Rockefeller University and lab members of Dr. Takashi, Kyoto University for extending their help in genetic analysis of WNIN rats. Authors also thank the Director, National Institute of Nutrition for the support in this work. The work was funded by ICMR, INDIA and National Institutes of Health, USA (No. 63/2/INDO-US/2005-RHN). The funding agencies have no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Molecular Genetics Laboratory, National Centre for Laboratory Animal Science (NCLAS), National Institute of Nutrition (NIN), Tarnaka, Hyderabad, 500007, India

    Kiran Kumar Battula, Giridharan Nappanveettil & Rajender Rao Kalashikam

  2. Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Satoshi Nakanishi & Takashi Kuramoto

  3. Molecular Genetics Laboratory, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, 10065, USA

    Jeffry M. Friedman

Authors
  1. Kiran Kumar Battula
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giridharan Nappanveettil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Satoshi Nakanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Kuramoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeffry M. Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rajender Rao Kalashikam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajender Rao Kalashikam.

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Battula, K.K., Nappanveettil, G., Nakanishi, S. et al. Genetic Relatedness of WNIN and WNIN/Ob with Major Rat Strains in Biomedical Research. Biochem Genet 53, 132–140 (2015). https://doi.org/10.1007/s10528-015-9679-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-015-9679-8

Keywords

Search

Navigation