Goat (Capra aegagrus hircus)
The goat is a domestic ruminant mammal that belongs to the bovid family which includes sheep and cattle, among others. Its domestication dates back about ten millennia..
Goats are gaining acceptance as an established model for biomedical research and for surgical training and teaching. They are used in medical, orthopedic, psychological, chemotherapeutic, and physiologic research. Prions, the protein that plays a major role in mad cow disease and Creutzfeldt-Jacob disease, were first discovered in sheep and goats. This research was awarded a Nobel Prize in 1997.
Goats can be gentle, easy to handle and transport, intelligent, affectionate, friendly, and clean, and they appear to be hardier than other members of the ruminant family. Compared with cattle, their small size permits goats to be maintained in a relatively small area.
The sgoat genome hasn’t been sequenced yet, but the bovine genome and the sheep genome have and these resources have been used to facilitate work in the goat.
Using a big animal, but not too big
Large animal research opens up the possibility of taking frequent biopsies and samples, obtain many more cells from one sample, as well as the option to insert catheters into multiple blood vessels. This cannot be done in small animals such as rodents.
The similarity in organ size between some large animal models and humans means they are better models for surgery, heamodynamics, and perhaps one day as a source of xenotransplants
Large animals can be used for “pharming” to produce large quantities of useful proteins in the milk of transgenic cows, pigs, sheep, or goats, such as a1-antitrypsin produced in sheep milk for patients with pulmonary emphysema who lack this enzyme.
Moreover, a unique advantage to using livestock or companion animal species is that it also allows for “dual-purpose” research. That is research that not only benefits human health by greater understanding of biological processes, but can also advance animal agriculture so that we have a continued supply of abundant, safe, affordable, and high quality meat and dairy products.
As other large animal models are becoming more costly and difficult to procure, the research community must search for suitable alternatives. Often existing runs, kennels, and transport cages designed for other larger traditional laboratory animals (such as dogs and swine) can be easily modified for goats. The friendly and docile nature of the goat can make it a desirable animal model for research and teaching programs.
The study of human disease
Several naturally occurring diseases in goats make them suitable animal models for the study of some human diseases. Goats infected with the caprine arthritis encephalitis virus (CAEV) are used as a natural disease model for chronic rheumatoid arthritis of humans. CAEV is a retrovirus related to the HIV retrovirus. Myotonia congenita occurs in different breeds of goats, which are used as experimental models for studies on human myotonia. Pygmy goats are considered to be good antibody producers in immunological research.
Surgical training and teaching
Due to public sentiment and increasing costs associated with using dogs, some veterinary schools and physician training programs have replaced the dog with the goat in surgical training labs. The goat has been used extensively as an animal model for biomaterials research, teaching, and testing.
Farming and Pharming
Recent literature has described the importance of the development of transgenic farm animals. Preliminary research has focused on altering phenotype to increase the animal's growth rate and improve the carcass composition by reducing fat content for example. Transgenic techniques are currently being applied with the goal of creating a transgenic small ruminant capable of producing large quantities of human pharmaceuticals through synthesis of recombinant proteins excreted though the milk.
A natural mutation has appeared in some goat, responsible for both the absence of horns and sexual inversion of male types to XX. For the last 15 years at least, goats have therefore been used as a model to study the differentiation of gonads.
The first major gene for ovarian differentiation in mammals (FOXL2 gene) was discovered in goats. The absence of this gene leads to the early differentiation of testicles in mutated animals.
The use of a big animal can have its advantages, including for reproductive research. One example is the ability to catheterize both the maternal and foetal vasculature during pregnancy. This allows researchers to obtain multiple samples throughout gestation under different experimental conditions in order to study transfer across the placenta for exmple. Another advantage is the ability to non-invasively monitor ovarian development by ultrasound, and take samples from ovarian follicles after different treatments, without having to sacrifice the animal.
Research into Q fever
Between 2007 and 2010 the Netherlands was confronted with the largest Q fever outbreak ever reported, which resulted in more than 4000 human cases.
Q fever is a bacterial infection that can be spread to humans by infected animals most commonly by sheep, cattle and goats. Most people with Q fever will either have no symptoms, or will only have mild flu-like symptoms that pass within two weeks. However, the symptoms can sometimes last several months, and occasionally the infection can lead to life-threatening problems if it spreads to other parts of the body, such as the heart. If you get Q fever while pregnant, your baby may be born early or have a low birthweight, and there is a risk of having a miscarriage or stillbirth.
To gain insight into the risk Q fever infected goats pose for humans, research was initiated to study the pathogenesis of the bacterium in pregnant and non-pregnant goats. This Q fever goat model provided new insights into the excretion of the bacterium as well as potential additional risks for humans. This focused the control measures. It is recommended to avoid contact with animals, especially while animals are giving birth and to not consume raw milk or raw milk products.
Comparison of the innate immunity in goats and humans as well as Q fever bacterium genomics are still being studied to gain a better understanding of the bacterium and its interactions with human and animal hosts in order to develop better control measures, and to improve the treatment of acute and chronic Q fever human patients.
Transgenic goats can be used to produce a wide variety of biologically active recombinant proteins and antibodies. They include both small and large proteins as well as complex glycosylated proteins containing specific sugars attached at precise sites in the mature protein molecule.
The types of antibodies that can be created using transgenic animals include mouse antibodies, partially humanized antibodies, and fully human antibodies. Any type of protein can be produced, notably anticoagulant proteins and proteins that can be fused to the targeting sequence of an anti-tumour antibody, for example.
Transgenic animals were first developed in 1985 and were useful in the production of biopharmaceuticals shortly thereafter as the animals express the desired protein in their milk in sufficient quantity and quality. The ideal transgenic animal produces plenty of milk, where the protein is produced, and has relatively short generation times. Typically, dairy animals are used because of their high volume of milk production. Goats have been selected for a number of reasons, the chief of which is the short generational time of 18 months.
Goats produce about 800 litres of milk per year. Using goats has been shown to dramatically increase the yield of the active protein by more than 10 times that produced from cell culture
The key to this method of drug development is the use of the mammary gland. The major function of the mammary gland is to produce a solution that is loaded with a variety of proteins, some of which are difficult or impossible to create in tissue culture-based bioreactors. Also, the mammary gland is capable of processing completed proteins through glycosylation and gamma carboxylation, functions that occur after translation of the DNA into proteins.
Transgenically produced proteins are isolated from milk in a multistep process that includes methods normally used by cell culture bioreactors as well as processes adapted from the dairy industry. The resulting proteins are held to the same standards as any other recombinant protein. Obviously safety concerns have been addressed: All goats are certified to be free of scrapie by the United States Department of Agriculture, the farm is inspected by the FDA, and the goats receive thorough veterinary care.
A total of 214 experimental procedures used goat for research in 2016 in the UK.