Transgenic Rabbit Service

Why use rabbits?
Although the study of many human diseases has benefited
significantly from the use of mouse models 1, small
rodents do not always accurately reflect human physiology
2,3.
Take the cardiovascular system as an example. The length of the
mouse’s cardiac cycle is only one-tenth of that of the human. The
high-density lipoproteins (HDL) are the predominant form of
lipoproteins in the mouse plasma in contrast to the low-density
lipoproteins (LDL) that are predominant in humans, conferring
resistance to diet-induced atherosclerosis.
The rabbit
would be an ideal choice
(Table 1)2-4,
considering the following: 1) Rabbit ventricles are similar to
humans’ and both a- and β-MHC isoforms are expressed with β-MHC
being the predominant isoform in adults; 2) Rabbit lipoprotein
metabolism is very similar to that of humans (e.g., LDL-mammals,
same as humans), but very different from mice (HDL-mammals); 3)
Cholesteryl ester transfer protein (CETP), which plays a central
role in the atherosclerotic process, is abundant in both human and
rabbit plasma but absent in the mouse; 4) Like humans, rabbits are
very susceptible to diet-induced atherosclerosis.
Comparing to mice, rabbits are phylogenetically closer to human.
Because of the anatomical, physiological, genetic and biochemical
similarities between the rabbit and the human, this species is
preferentially used in pulmonary, cardiovascular and metabolic
studies, including airway obstructive disease, embolic stroke,
arteriosclerosis, cholera, cystic fibrosis, neoplasia, diabetes,
acute respiratory distress syndrome, malignant lymphoma, acquired
immunodeficiency syndrome and hypercalcemia of malignancy.
As a classical experimental animal species, rabbit has several other
advantages over some other animal species (e.g., monkey, pigs).
It has a short gestation period (30-31 days), large litter size
(4-12/litter) and can be housed conveniently in an indoor facility.
In addition to the use as an animal model, rabbit is also used for
drug screening, antibody production, and the production of
therapeutic proteins (bioreactors). Some proteins can be
properly synthesized in rabbit milk, but not in other animal systems
(e.g. cattle or goats) due to the post translation processing.
Table 1.
Selected Differences of Heart Physiology Between Mouse, Rabbit and
Human (modified from 3 )
|
|
Mouse |
Rabbit |
Human |
|
Cardiac Sarcomere Composition |
a-
myosin heavy chain (MHC) |
b-MHC |
b-MHC |
|
Lipoprotein Profile |
HDL-rich |
LDL-rich |
LDL-rich |
|
CETP |
No |
Yes |
Yes |
|
Dietary Cholesterol |
Resistant |
Sensitive |
Sensitive |
|
Atherosclerosis |
Resistant |
Susceptible |
Susceptible |
References
1
K. L. Svenson, M. A. Bogue, and L. L. Peters, J Appl Physiol
94 (4), 1650 (2003); A. Wessels and D. Sedmera, Physiol
Genomics 15 (3), 165 (2003).
2
J. F. James, T. E. Hewett, and J. Robbins, Circ Res 82
(4), 407 (1998); J. James, Y. Zhang, K. Wright et al., J Mol Cell
Cardiol 34 (7), 873 (2002).
3
J. Fan and T. Watanabe, Pharmacol Ther 99 (3), 261
(2003).
4
Z. Bosze, L. Hiripi, J. W. Carnwath et al., Transgenic Res
12 (5), 541 (2003).
|