Studying the Genetics of Complex But Common Human Diseases Using Mice

  • Nobuyo Maeda
  • Oliver Smithies
Conference paper
Part of the Serono Symposia USA book series (SERONOSYMP)


Cardiovascular and cerebrovascular diseases that result from atherosclerosis and hypertension account for a large proportion of morbidity and mortality in the United States. Females are generally less susceptible to these conditions until after menopause, when they rapidly become as susceptible as males. In addition to gender, the genetic makeup of an individual is clearly important in the etiology of these diseases, and genetic analyses based on human population and family studies have successfully identified various factors associated with atherosclerosis and with hypertension thanks to the advancement of molecular techniques. The genetic heterogeneity of humans, however, makes it difficult to dissect the roles of individual genetic factors and to determine fundamental cause and effect relationships. In addition, environmental factors that significantly influence the development of these diseases are difficult to control in humans.


Atrial Natriuretic Peptide Guanylyl Cyclase Natriuretic Peptide Receptor Human APOE Common Human Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Smithies O, Kim H-S. Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice. Proc Natl Acad Sci USA 1994; 91:3612–15.PubMedCrossRefGoogle Scholar
  2. 2.
    Flynn TG, de Bold ML, de Bold AJ. The amino acid sequence of an arterial peptide with potent diuretic and natriuretic properties. Biochem Biophys Res Commun 1983;90:859–65.CrossRefGoogle Scholar
  3. 3.
    Garbers DL, Lowe DG. Guanylyl cyclase receptors. J Bio Chem 1994;269: 30741–44.Google Scholar
  4. 4.
    Oliver PM, John SWM, Purdy KE, Kim R, Maeda N, Goy MF, et al. Natriuretic peptide receptor 1 expression influences blood pressures of mice in a dose-dependent manner. Proc Natl Acad Sci USA 1998;95:2547–51.PubMedCrossRefGoogle Scholar
  5. 5.
    Oliver PM, Fox JE, Kim R, Rockman HA, Kim H-S, Smithies O, et al. Hypertension, cardiac hypertrophy and sudden death in mice lacking natriuretic peptide receptor A. Proc Natl Acad Sci USA 1997;94:14730–35.PubMedCrossRefGoogle Scholar
  6. 6.
    Mahley RW, Rall SC Jr. Type III hyperlipoproteinemia (dysbetalipoproteinemia): the role of apolipoprotein E in normal and abnormal lipoprotein metabolism. In: Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited diseases, seventh ed. New York: McGraw-Hill, 1995:1953–80.Google Scholar
  7. 7.
    Hixon JE. Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathological determination of atherosclerosis in youth (PDAY) research group. Arterioscler Thromb 1991;11:1237–44.CrossRefGoogle Scholar
  8. 8.
    Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993;261:921–23.Google Scholar
  9. 9.
    Sullivan PM, Mezdour H, Aratani Y, Knouff C, Najib J, Reddick R, et al. Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J Biol Chem 1997;272:17971 80.CrossRefGoogle Scholar
  10. 10.
    Sullivan PM, Mezdour H, Quarfordt SH, Maeda N. Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human APOE*2 . J Clin Invest 1998;102:130–35.Google Scholar
  11. 11.
    Reddick RL, Zhang SH, Maeda N. Atherosclerosis in mice lacking apoE. Arterioscler Thromb 1994;14:141–47.PubMedCrossRefGoogle Scholar
  12. 12.
    McGill HC Jr, Strong JP, Tracy RE, McMahan CA, Oalmann MC. Relation of a postmortem renal index of hypertension to atherosclerosis in youth. The pathological determinants of atherosclerosis in youth (PDAY) research group. Arterioscler Thromb Vasc Biol 1995;15:2222–28.PubMedCrossRefGoogle Scholar
  13. 13.
    Chobanian AV, Lichtenstein AH, Nilakhe V, Haudenschild CC, Drago R, Nickerson C. Influence of hypertension on aortic atherosclerosis in the Watanabe rabbit. Hypertension 1989;14:203–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Shesely EG, Maeda N, Kim S-S, Desai KM, Krege JH, Lauback VE, et al. Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci USA 1996;93:13176–81.PubMedCrossRefGoogle Scholar
  15. 15.
    Kim H-S, Krege JH, Kluckman KD, Hagaman JR, Hodgin JB, Best CF, et al. Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci USA 1995;92:2735–39.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 2000

Authors and Affiliations

  • Nobuyo Maeda
  • Oliver Smithies

There are no affiliations available

Personalised recommendations