Severe combined immunodeficiency (non-human)
Encyclopedia
Severe Combined Immunodeficiency (SCID) is a severe immunodeficiency
genetic disorder
that is characterized by the complete inability of the adaptive immune system to mount, coordinate, and sustain an appropriate immune response, usually due to absent or atypical T
and B
lymphocyte
s. In humans, SCID is colloquially known as "bubble boy" disease
, as victims may require complete clinical isolation to prevent lethal infection from environmental microbes.
Several forms of SCID occur in animal species. Not all forms of SCID have the same cause; different genes and modes of inheritance have been implicated in different species.
recessive disorder that affects the Arabian horse
. Similar to the "bubble boy" condition in humans, an affected foal
is born with no immune system, and thus generally dies of an opportunistic infection, usually within the first four to six months of life. There is a DNA
test that can detect healthy horses who are carriers of the gene causing SCID, thus testing and careful, planned matings can now eliminate the possibility of an affected foal
ever being born.
SCID is one of six genetic diseases known to affect horses of Arabian bloodlines, and the only one of the six for which there is a DNA
test to determine if a given horse is a carrier of the allele
. There are other genetic diseases that affect other horse breeds, and horses of part-Arabian bloodlines can be carriers of SCID.
Unlike SCID in humans, which can be treated, for horses, to date, the condition remains a fatal disease. When a horse is heterozygous for the gene, it is a carrier, but perfectly healthy and has no symptoms at all. If two carriers are bred together, however, classic Mendelian genetics indicate that there is a 50% chance of any given mating producing a foal that is a carrier heterozygous for the gene, and a 25% risk of producing a foal affected by the disease. If a horse is found to carry the gene, the breeder can choose to geld
a male or spay a female horse so that they cannot reproduce, or they can choose to breed the known carrier only to horses that have been tested and found to be "clear" of the gene. In either case, careful breeding practices can avoid ever producing an SCID-affected foal.
form that is very similar to X-SCID
in humans, and an autosomal recessive form that is similar to the disease in Arabian horses and SCID mice.
X-SCID in dogs is seen in Basset Hound
s and Cardigan Welsh Corgi
s. Because it is an X-linked disease, females are carriers only and disease is seen in males exclusively. It is caused by a mutation in the gene for the cytokine receptor common gamma chain
. Recurring infections are seen and affected animals usually do not live beyond three to four months. Characteristics include a poorly developed thymus gland, decreased T-lymphocytes and IgG
, absent IgA
, and normal quantities of IgM
. A common cause of death is canine distemper
, which develops following vaccination
with a modified live
distemper virus vaccine. Due to its similarity to X-SCID in humans, breeding colonies of affected dogs have been created in order to study the disease and test treatments, particularly bone marrow transplantation and gene therapy
.
The autosomal recessive form of SCID has been identified in one line of Jack Russell Terrier
s. It is caused by a loss of DNA protein kinase
, which leads to faulty V(D)J recombination
. V(D)J recombination is necessary for recognition of a diverse range of antigen
s from bacteria, viruses, and parasites. It is characterized by nonfunctional T and B-lymphocytes and a complete lack of gammaglobulins. Death is secondary to infection. Differences between this disease and the form found in Bassets and Corgis include a complete lack of IgM and the presence of the disease in females.
s for research into the basic biology of the immune system
, cell transplantation strategies, and the effects of disease on mammalian systems. They have been extensively used as hosts for normal and malignant
tissue transplants. In addition, they are useful for testing the safety of new vaccines or therapeutic agents in immunocompromised individuals.
The condition is due to a rare recessive mutation on Chromosome 16 responsible for deficient activity of an enzyme involved in DNA repair (Prkdc or "protein kinase, DNA activated, catalytic polypeptide"). Because V(D)J recombination
does not occur, the humoral and cellular immune systems fail to mature. SCID mice, therefore, present with impaired ability to make T or B lymphocytes, or activate some components of the complement system
, and cannot efficiently fight infections, nor reject tumors and transplants.
By crossing SCID mice with mice carrying mutations in related genes, such as interleukin
-2Rgamma, more efficient immunocompromised strains can be created to further aid research. The degree to which the various components of the immune system are compromised varies according to what other mutations the mice carry along with the SCID mutation.
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
that is characterized by the complete inability of the adaptive immune system to mount, coordinate, and sustain an appropriate immune response, usually due to absent or atypical T
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
and B
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s. In humans, SCID is colloquially known as "bubble boy" disease
Severe combined immunodeficiency
Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
, as victims may require complete clinical isolation to prevent lethal infection from environmental microbes.
Several forms of SCID occur in animal species. Not all forms of SCID have the same cause; different genes and modes of inheritance have been implicated in different species.
Horses
Equine SCID is an autosomalAutosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive disorder that affects the Arabian horse
Arabian horse
The Arabian or Arab horse is a breed of horse that originated on the Arabian Peninsula. With a distinctive head shape and high tail carriage, the Arabian is one of the most easily recognizable horse breeds in the world. It is also one of the oldest breeds, with archaeological evidence of horses...
. Similar to the "bubble boy" condition in humans, an affected foal
Foal
A foal is an equine, particularly a horse, that is one year old or younger. More specific terms are colt for a male foal and filly for a female foal, but these terms are used until the horse is age three or four. When the foal is nursing from its dam , it may also be called a suckling...
is born with no immune system, and thus generally dies of an opportunistic infection, usually within the first four to six months of life. There is a DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
test that can detect healthy horses who are carriers of the gene causing SCID, thus testing and careful, planned matings can now eliminate the possibility of an affected foal
Foal
A foal is an equine, particularly a horse, that is one year old or younger. More specific terms are colt for a male foal and filly for a female foal, but these terms are used until the horse is age three or four. When the foal is nursing from its dam , it may also be called a suckling...
ever being born.
SCID is one of six genetic diseases known to affect horses of Arabian bloodlines, and the only one of the six for which there is a DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
test to determine if a given horse is a carrier of the allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
. There are other genetic diseases that affect other horse breeds, and horses of part-Arabian bloodlines can be carriers of SCID.
Unlike SCID in humans, which can be treated, for horses, to date, the condition remains a fatal disease. When a horse is heterozygous for the gene, it is a carrier, but perfectly healthy and has no symptoms at all. If two carriers are bred together, however, classic Mendelian genetics indicate that there is a 50% chance of any given mating producing a foal that is a carrier heterozygous for the gene, and a 25% risk of producing a foal affected by the disease. If a horse is found to carry the gene, the breeder can choose to geld
Gelding
A gelding is a castrated horse or other equine such as a donkey or a mule. Castration, and the elimination of hormonally driven behavior associated with a stallion, allows a male horse to be calmer and better-behaved, making the animal quieter, gentler and potentially more suitable as an everyday...
a male or spay a female horse so that they cannot reproduce, or they can choose to breed the known carrier only to horses that have been tested and found to be "clear" of the gene. In either case, careful breeding practices can avoid ever producing an SCID-affected foal.
Dogs
There are two known types of SCID in dogs, an X chromosome-linkedSex linkage
Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance...
form that is very similar to X-SCID
X-SCID
X-linked severe combined immunodeficiency is an immunodeficiency disorder that affects lymphocytes. It is a recessive trait stemming from a defective version of the gene responsible for the functionality of the Interleukin 2 receptor ....
in humans, and an autosomal recessive form that is similar to the disease in Arabian horses and SCID mice.
X-SCID in dogs is seen in Basset Hound
Basset Hound
The Basset Hound is a short-legged breed of dog of the hound family. They are scent hounds, bred to hunt rabbits and hare by scent. Their sense of smell for tracking is second only to that of the Bloodhound....
s and Cardigan Welsh Corgi
Cardigan Welsh Corgi
The Cardigan Welsh corgi is one of two separate dog breeds known as Welsh corgis that originated in Wales, the other being the Pembroke Welsh corgi. It is one of the oldest herding breeds.-Characteristics:...
s. Because it is an X-linked disease, females are carriers only and disease is seen in males exclusively. It is caused by a mutation in the gene for the cytokine receptor common gamma chain
Common gamma chain
The common gamma chain , also known as interleukin-2 receptor subunit gamma or IL-2RG, is a cytokine receptor sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4, IL-7, IL-9, IL-15 and interleukin-21 receptor...
. Recurring infections are seen and affected animals usually do not live beyond three to four months. Characteristics include a poorly developed thymus gland, decreased T-lymphocytes and IgG
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
, absent IgA
Immunoglobulin A
Immunoglobulin A is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined; between three and five grams are secreted into the intestinal lumen each day....
, and normal quantities of IgM
Immunoglobulin M
Immunoglobulin M, or IgM for short, is a basic antibody that is produced by B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system...
. A common cause of death is canine distemper
Canine distemper
Canine distemper is a viral disease that affects animals in the families Canidae, Mustelidae, Mephitidae, Hyaenidae, Ailuridae, Procyonidae, Pinnipedia, some Viverridae and Felidae...
, which develops following vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
with a modified live
Attenuated virus
An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable . Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the virus .-Examples:Examples of...
distemper virus vaccine. Due to its similarity to X-SCID in humans, breeding colonies of affected dogs have been created in order to study the disease and test treatments, particularly bone marrow transplantation and gene therapy
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
.
The autosomal recessive form of SCID has been identified in one line of Jack Russell Terrier
Jack Russell Terrier
The Jack Russell terrier is a small terrier that has its origins in fox hunting. It is principally white-bodied smooth, rough or broken-coated which is commonly confused with the Parson Russell terrier and the Russell terrier with the term "Jack Russell" commonly misapplied to other small white...
s. It is caused by a loss of DNA protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
, which leads to faulty V(D)J recombination
V(D)J recombination
VJ recombination, also known as somatic recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin and T cell receptors production of the immune system...
. V(D)J recombination is necessary for recognition of a diverse range of antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s from bacteria, viruses, and parasites. It is characterized by nonfunctional T and B-lymphocytes and a complete lack of gammaglobulins. Death is secondary to infection. Differences between this disease and the form found in Bassets and Corgis include a complete lack of IgM and the presence of the disease in females.
Mice
SCID mice are routinely used as model organismModel organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...
s for research into the basic biology of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, cell transplantation strategies, and the effects of disease on mammalian systems. They have been extensively used as hosts for normal and malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
tissue transplants. In addition, they are useful for testing the safety of new vaccines or therapeutic agents in immunocompromised individuals.
The condition is due to a rare recessive mutation on Chromosome 16 responsible for deficient activity of an enzyme involved in DNA repair (Prkdc or "protein kinase, DNA activated, catalytic polypeptide"). Because V(D)J recombination
V(D)J recombination
VJ recombination, also known as somatic recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin and T cell receptors production of the immune system...
does not occur, the humoral and cellular immune systems fail to mature. SCID mice, therefore, present with impaired ability to make T or B lymphocytes, or activate some components of the complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
, and cannot efficiently fight infections, nor reject tumors and transplants.
By crossing SCID mice with mice carrying mutations in related genes, such as interleukin
Interleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...
-2Rgamma, more efficient immunocompromised strains can be created to further aid research. The degree to which the various components of the immune system are compromised varies according to what other mutations the mice carry along with the SCID mutation.
See also
- Severe Combined ImmunodeficiencySevere combined immunodeficiencySevere combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
, for a detailed overview of the condition in humans and an in-depth scientific explanation of the disease - Arabian horseArabian horseThe Arabian or Arab horse is a breed of horse that originated on the Arabian Peninsula. With a distinctive head shape and high tail carriage, the Arabian is one of the most easily recognizable horse breeds in the world. It is also one of the oldest breeds, with archaeological evidence of horses...
- Animal testing on rodentsAnimal testing on rodentsRodents are commonly used in animal testing, particularly guinea pigs, hamsters, gerbils, rats, and mice.-The statistics:In the UK in 2004, 1,910,110 mice, 464,727 rats and 37,475 other rodents were used...