Biomedical Models: The Mouse


Contents


Author: Maria Currie
Student, Dalhousie University
December, 2001 		mice
   Photo courtesy of Bill Branson

The mouse (Mus musculus) is widely used as a mammalian model for biomedical research in the area of human health.

This page provides an overview of the mouse as a biomedical model and a gateway to more detailed information.

The page was prepared as a contribution to a Website on biomedical models.



1. Overview

Small but Mighty
The benefits of mice as biomedical models
  • Small size
  • High fertility rate
  • Cost-efficiency
  • Genetic manipulability
  • Genetic similarity to humans
mice
Photo courtesy of Dr. Sylvia Craig,
Dalhousie University

Of Mice and Men
The genetic similarities between mice and humans
Gene for gene, mice and humans are very similar. In fact, both mice and humans have the same number of nucleotides in their genomes.

Approximately, three billion base pairs make up the mouse and human genomes. Similarities between mice and humans genes range from about 7 percent to 90 percent, with an average of about 85 percent similarity (*FUNCTIONAL AND COMPARATIVE GENOMICS FACT SHEET, 2001). Therefore, some protein products are almost identical in both mice and humans.

The average 15 percent nucleotide difference between mice and human genes consist of mainly neutral genes that do not alter proteins significantly. However, some lead to subtle changes, while others have dramatic effects that ultimately distinguish us from mice.

Strains of Mice Used in Biomedical Research

This table summarizes key characteristics of some major types or strains of mice used in biomedical research. (Source: *UC CENTER FOR ANIMAL ALTERNATIVES)

Type Characteristics
Inbred
  • Genetically identical due to inbreeding
  • Predisposed to genetic defects and diseases
Transgenic
  • Genetically engineered
  • Genetically altered by the injection of one or more genes
Immunodeficient
  • Minimal immune function
    • Nude mice
    • Mice with Severe Combined Immune Deficiency (SCID)
  • Used in cancer and AIDS research
Knockout
  • Genetically engineered to lack a specific gene
Germfree
  • Free from all detectable viruses, bacteria and parasites


Recent Biomedical Applications of Mice Models

The development of mice as genetic models has enabled scientists to study the pathology of specific genetic defects that occur in humans. Below, recent examples are cited.

Disease Pathology of the Disease Research
Sickle-Cell Disease An inherited disorder in which elongated red blood cells aggregate in veins where oxygen in low. As a result, tissues suffer severe damage due to oxygen deficiency. A mouse model of the disease formed by transgene insertions has allowed researchers to study possible treatments that hinder sickling, such as nitric oxide breathing(Martinez-Ruiz et al., 2001).
Diabetes Type I diabetes mellitus is an autoimmune disorder in which immune cells attack insulin-producing pancreas cells. Non-obese diabetic mouse models (NOD) were used to identify the self-peptides that trigger the type I autoimmune response(Bonifacio et al., 2001).
Human Gastric Cancer An uncontrolled growth and division of cancerous cells in the stomach. This disease has a very poor prognosis with only a five year survival rate. SCID mice that had been administered antisense oligonucleotides were used to prove that the treatment enhanced chemotherapy by significantly reducing tumour size and patient survival (Wacheck, 2001).
Cleft Palate This birth defect is characterized by the failure of the roof of the mouth to completely develop. A mouse model of cleft palate was found to result from a defect in the gene cp1. This model was recently used in the study of in utero treatment possibilities for cleft palate(Erfani et al., 2001).

2. Glossary

Antisense oligonucleotides
The long sequence of DNA or RNA that is complementary to the coding strand. (Source: adapted from Klug et al., 2000, p.373-373)
Severe Combined Immune Deficiency (SCID)
Patients with SCID have no functional immune system. It is caused by a genetic mutation. (Source: adapted from Klug et al., 2000, p.587)
Transgene Insertion
The modification of an organisms genome by the introduction of external DNA sequences. (Source: adapted from Klug et al., 2000, p.771)

3. Useful Links

  • FUNCTIONAL AND COMPARATIVE GENOMICS FACT SHEET (http://www.ornl.gov/hgmis/faq/compgen.html). U.S. Department of Energy Office of Science, Office of Biological and Environmental Research, Human Genome Program, Spons. (Mod. 200, August 16; Viewed 31 Oct. 2001). This site provides an overview of functional genetics and links to research involving mice and other genetic model organisms.

  • MODEL ORGANISMS FOR BIOMEDICAL RESEARCH (http://www.nih.gov/science/models/). National Institutes of Health, Spons. (Viewed  31 Oct.  2001).
    This site provides links to research using mammalian and non-mammalian models. The link to mouse model information includes recent developments in regulations for mouse model use.

  • MOUSE GENOME INFORMATICS(MGD) (http://www.informatics.jax.org/) The Jackson Laboratory, Spons. (Mod.  2001, November 2; Viewed 3 Nov. 2001).
    This site provides links to additional information on biomedical research including genetic maps. It is sponsored by Jackson Laboratories, a supplier of mice for research.

  • UC CENTER FOR ANIMAL ALTERNATIVES (http://www.vetmed.ucdavis.edu/Animal_Alternatives/cancer.htm). University of California Davis School for Veterinary Medicine, Spons. (Mod.  2001, September 27; Viewed 3 Nov.  2001).
    This site outlines current information on mice as genetic models for cancer research.

4. Useful Literature

  • Bonifacio E, Atkinson M, Eisenbarth G, Serreze D, Kay TW, Lee-Chan E, Singh B. 2001. International Workshop on Lessons From Animal Models for Human Type 1 Diabetes: Identification of Insulin but Not Glutamic Acid Decarboxylase or IA-2 as Specific Autoantigens of Humoral Autoimmunity in Nonobese Diabetic Mice. Diabetes 50(11): 2451-2458.

  • Erfani S, Maldonado TS, Crisera CA, Warren SM, Lee S, Longaker MT. 2001. An in vitro mouse model of cleft palate: defining a critical intershelf distance necessary for palatal clefting. Plastic and Reconstructive Surgery108(2): 403-410. http://www.plasreconsurg.com

  • Haddad, Gabriel G., Xu, Tian. 2001. Genetic models in cardiorespiratory biology M. Dekker, New York. Novanet: Dal. Lib. WF 600 L963.

  • Klug, W., Cummings, M. 2000. Concepts of Genetics, Sixth Edition. Prentice Hall, New Jersey. Novanet: Dal. Lib. QH430 K574.

  • Martinez-Ruiz R, Montero-Huerta P, Hromi J, Head CA. 2001. Inhaled nitric oxide improves survival rates during hypoxia in a sickle cell (SAD) mouse model. Anesthelsiology 94(6): 1113-1118. http://www.anesthesiology.org

  • Sundberg, John P., and Boggess, Dawnalyn. 2000. Systematic approach to evaluation of mouse mutations CRC Press, Boca Raton, Florida, USA. Novanet: Dal Lib. QY 60 R6 S995.

  • Wacheck V, Heere-Ress E, Halaschek-Wiener J, Lucas T, Meyer H, Eichler HG, Jansen B. 2001. Bcl-2 antisense oligonucleotides chemosensitize human gastric cancer in a SCID mouse xenotransplantation model. Journal of Molecular Medicine 79(10): 587-593.

5. Useful Journals

6. Cited Literature and Links

  • Bonifacio E, Atkinson M, Eisenbarth G, Serreze D, Kay TW, Lee-Chan E, Singh B. 2001. International Workshop on Lessons From Animal Models for Human Type 1 Diabetes: Identification of Insulin but Not Glutamic Acid Decarboxylase or IA-2 as Specific Autoantigens of Humoral Autoimmunity in Nonobese Diabetic Mice. Diabetes 50(11): 2451-2458.

  • Erfani S, Maldonado TS, Crisera CA, Warren SM, Lee S, Longaker MT. 2001. An in vitro mouse model of cleft palate: defining a critical intershelf distance necessary for palatal clefting. Plastic and Reconstructive Surgery108(2): 403-410. http://www.plasreconsurg.com

  • Klug, W., Cummings, M. 2000. Concepts of Genetics, Sixth Edition. Prentice Hall, New Jersey. Novanet: Dal. Lib. QH430 K574.

  • Martinez-Ruiz R, Montero-Huerta P, Hromi J, Head CA. 2001. Inhaled nitric oxide improves survival rates during hypoxia in a sickle cell (SAD) mouse model. Anesthelsiology 94(6): 1113-1118. http://www.anesthesiology.org

  • Wacheck V, Heere-Ress E, Halaschek-Wiener J, Lucas T, Meyer H, Eichler HG, Jansen B. 2001. Bcl-2 antisense oligonucleotides chemosensitize human gastric cancer in a SCID mouse xenotransplantation model. Journal of Molecular Medicine 79(10): 587-593.

  • FUNCTIONAL AND COMPARATIVE GENOMICS FACT SHEET (http://www.ornl.gov/hgmis/faq/compgen.html). U.S. Department of Energy Office of Scinece, Office of Biological and Environmental Research, Human Genome Program, Spons. (Mod. 2001, August 16;  Viewed 31 Oct.  2001).

  • MODEL ORGANISMS FOR BIOMEDICAL RESEARCH (http://www.nih.gov/science/models/). National Institutes of Health, Spons. (Viewed  31, Oct. 2001).

  • MOUSE GENOME INFORMATICS(MGD) (http://www.informatics.jax.org/) The Jackson Laboratory, Spons. (Mod. 2001, November 2; Viewed  3 Nov.  2001).

  • UC CENTER FOR ANIMAL ALTERNATIVES (http://www.vetmed.ucdavis.edu/Animal_Alternatives/cancer.htm). University of California Davis School for Veterinary Medicine, Spons. (Mod. 2001, September 27; Viewed November 3, 2001).

    Image credits, gratefully acknowledged

  • Top photograph of 2 mice: MODEL ORGANISMS FOR BIOMEDICAL RESEARCH (http://www.nih.gov/science/models/) .Courtesy Bill Branson, Medical Arts and Photography Branch, Office of Research Services, National Institutes of Health, U.S.A.

  • Photograph of white mice: Dr. Sylvia Craig, Dalhousie Unversity

  • Background Image: AAA - Backgrounds - Free Backgrounds
    (http://www.aaa-backgrounds.com)


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