it is an informative ppt

1. Module IV
• Transgenic Mice as a Model for Human Diseases
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2. Transgenic Mice as a Model for Human Diseases
Introduction
• Transgenic technology has greatly influenced the focus and direction pace of biomedical research.
• Introduction of foreign DNA into the genome of animals by microinjection into fertilized oocytes is
now used in almost every field of research spanning from oncology, immunology and neurology to
cardiovascular medicine.
• The ability to integrate genes in the germ line and their successful expression in the host provides
an opportunity to study the role of a certain gene in the initiation and propagation of disease.
• Transgenic methodology serves as the link between molecular biology, introducing in vitro a
defined genetic modification and whole animal physiology, with the resulting in vivo alteration of
body function.
• This potential has been exploited to study the pathophysiological role of human genes.
• Transgenic animals have been used to study aspects of tumor development, immune regulation,
cardiovascular development and atherosclerosis.
• These studies have provided new insights into the genetic origin of certain diseases and have
improved our understanding of pathological processes on the cellular level.
• As a future goal, these studies may also serve the development of new diagnostic tools or novel
therapeutic strategies such as gene therapy.

3. Why are mice models used to study human diseases?
• Mice are the most commonly used animal model for studying human disease,
because they share mammalian features with humans.
• Mice are biologically very similar to humans and get many of the same
diseases, for the same genetic reasons.
• When it comes to protein-encoding genes, mice are 85 per cent similar to
humans. For non-coding genes, it is only about 50 per cent.
• Mice can be genetically manipulated to mimic virtually any human disease or
condition.
• Transgenic mouse models in toxicology have primarily been used to screen
drugs for carcinogenicity and to understand the mechanisms of toxicity.
• These mouse models can reliably predict the carcinogenic potential of
compounds and significantly reduce the risk of using these drugs in clinics to
treat human diseases.
• Mice are being used as models, for example, to study obesity, heart disease,
diabetes, arthritis, anxiety, ageing, Alzheimer's disease and Parkinson's
disease. They are also used to study different forms of cancer.

4. Transgenic Mice as models of neurodegenerative diseases in
humans
• Neurodegenerative diseases are of major socio-economic importance
and represent an enormous challenge for the scientific and medical
communities.
• Advances in molecular genetics during the past decade have begun to
provide approaches for the establishment of animal models for these
disorders using transgenic technology.
• Their analysis will lead to better understanding of disease
pathogenesis and will be invaluable for the identification of novel
diagnostic and therapeutic agents.
• With the current pace of genomic research, the generation of
transgenic mice, reproducing in full the pathology and symptoms of
even complex disorders such as Alzheimer's disease, must now be
considered achievable.

5. Genetically Engineered Animal Models
• Because the genetics and histology of xeno-grafts do not recapitulate
the genetics and histology of human tumors, genetically engineered
animal models were developed.
• The use of genetically modified mice for carcinogenicity evaluation
began more than 20 years ago, when researchers found that different
strains of genetically engineered mice demonstrated that cancer
incidence is increased and tumor latency is decreased in mice whose
germ line, the Ha-ras oncogene, has been inserted.
• Genetically modified animals are organisms in which specific genes
have been altered (added or ablated) to create models for human and
animal diseases. A transgenic animal is defined as an animal that
carries one or more foreign genes, deliberately introduced through
insertion into the animal's genome. The foreign gene is constructed
using recombinant deoxyribonucleic acid (DNA) technologies.

6. J Pharm Bioallied Sci. 2014 Jan-Mar; 6(1): 2–9.
• In a modern GEM (Genetically Modified Mice) models, oncogenes are activated
and/or tumor-suppressor genes (TSGs) are inactivated somatically, generally
through temporally controlled and tissue-specific expression of CRE recombinase
(tyrosine recombinase enzyme derived from the P1 Bacteriophage).
• Animals then develop tumors in the tissue of interest (in this case the lung). Tumor-
bearing genetically engineered mice are then treated with the compound of
interest and serially assessed for response.
The benefits of engineered mice are numerous. Examples include
1. Development and testing of safe and effective products for human application
(e.g., human antibodies).
2. The production of recombinant products (anti-coagulant; therapeutic antibodies).
3. A means to study disease mechanisms in a complex organism (diabetes).
4. Understanding the mechanistic causes and pathways underlying human disease, to
permit the development of efficient and targeted treatments (e.g., leukemia,
hypertension and obesity).