What is RAG deficiency?
RAG deficiency is considered an autosomal recessive disease. The disorder is generally identified in infants. Complete loss-of-function in RAG1/2, the main components responsible for V(D)J recombination activity, produces severe immunodeficiency in humans.
What would be the outcome of a deficiency in RAG genes?
Altered T and B cell development in patients with RAG gene defects is associated with impairment of immunological tolerance. Ultimately, the degree in the severity of T and B cell lymphopenia, breakage of immune tolerance, and exposure to environmental triggers are the main factors that shape the clinical phenotype.
What do RAG genes do?
The RAG1 gene provides instructions for making a member of a group of proteins called the RAG complex. This complex is active in immune system cells (lymphocytes) called B cells and T cells. These cells have special proteins on their surface that recognize foreign invaders and help protect the body from infection.
What is the RAG enzyme?
RAG enzymes work as a multi-subunit complex to induce cleavage of a single double stranded DNA (dsDNA) molecule between the antigen receptor coding segment and a flanking recombination signal sequence (RSS).
What are Rag knockout mice?
Rag1 knockout (Rag1 KO) mice have been extremely useful to study the role of the immune system in cancer, immunodeficiency disorders, inflammatory conditions, autoimmune diseases, lymphoid tissue pathologies, and graft versus host disease.
What is Rag in immunology?
Recombination activating genes (RAGs) encode enzymes that are involved in the rearrangement and recombination of the immunoglobulin and T cell receptor (TCR) genes during the process of VDJ recombination (Dudley et al., 2005).
What are RAG knockout mice?
What function does RAG1 and RAG2 perform?
Two proteins, RAG1 and RAG2, together form the nuclease that cleaves the DNA at the border of the signal sequences. Additional roles of these proteins in organizing the reaction complex for subsequent steps are explored.
Do Rag mice have T cells?
Rag1 null mice have no CD3+ or T cell receptor (TCR) alpha-beta positive cells. The thymus of the mutant mice contains 15 to 130 times fewer cells than heterozygous or wild-type siblings.
Do Rag mice have NK cells?
Indeed, NK cells are present in normal numbers in RAG-deficient mice, whereas T and B cells are completely absent (Mombaerts et al., 1992; Shinkai et al., 1992).
What is the pathophysiology of RAG2 deficiency?
RAG1 or RAG2 deficiency causes a form of autosomal recessive T-B-NK+ SCID. It accounts for approximately 4% of all SCID cases. 2. The enormous diversity of specific immunoglobulins/B cell receptors and T cell receptors is generated through a process of V (D)J recombination.
What is the history of RAG deficiency?
In humans, RAG deficiency was first recognised as a form of immune dysregulation known as Omenn syndrome. RAG deficiency is considered an autosomal recessive disease. The disorder is generally identified in infants.
What is Rag1 deletion?
Defects in this gene can cause several different diseases. Because of these effects, Rag1 deletion is used in mouse models of disease to impair T cell and B cell development, and functionally deletes mature T and B cells from the immune system. In humans, RAG deficiency was first recognised as a form of immune dysregulation known as Omenn syndrome.
What causes SCID in RAG1 deficiency?
Etiology SCID due to partial RAG1 deficiency is caused by hypomorphic mutation in the RAG1 gene (11p13). This results in oligoclonal expansion of T cell receptor (TCR) gamma-delta T cells and TCR alpha-beta T cell lymphopenia, although total lymphocyte counts are normal, in combination with CMV infection and autoimmunity.