Table XII.

Common Mouse Models of Immunodeficiency

Model	Immunodeficiency	Phenotype	Major uses
Nude mouse	Defective transcription factor gene controlling thymic epithelial cell differentiation	Athymic and hairless (unrelated but linked gene defect) No T cell functions	Tumor and xenograft studies
SCID mouse	Defective DNA-dependent kinase that recombines gene segments coding for T (TcR) and B (Ig) cell receptors	Hypoplastic lymphoid tissues No Ig or T cell responses Sensitive to ionizing radiation because of defective DNA break repair	V(D)J recombination studies Tumor and xenograft transplantation Lymphocyte subset transfer studies Reconstitution of human hematopoietic system (Hu-PBL-SCID)
Rag-1 and Rag-2 mice	Defective recombinase enzymes (Rag-1 and/or Rag-2), preventing formation of functional B a (Ig) and T (TcR) cell receptors	Hypoplastic lymphoid tissues No Ig or T cell responses	V(D)J recombination studies Tumor and xenograft transplantation Lymphocyte subset transfer studies
XID mouse	Defect in Bruton's tyrosine kinase gene affecting signal transduction in B cells	Decreased B cell numbers, low IgM Impaired response to polysaccharide antigens	Model for human X-lined agammaglobulinemia
Moth-eaten mouse	Defective phosphatase, impairing signal transduction from cell receptors	Deficient humoral and cellular immunity Lack cytotoxic T and NK cells Moth-eaten pelage secondary to folliculitis Autoimmune syndromes Hypergammaglobulinemia	Apoptosis studies Autoimmune syndromes
Beige mouse	Mutation on chromosome 13 affects pigment granules (coat, retina) and lysosomal granules of type II pneumocytes, mast cells, and NK cells	Diluted coat color Lysosomal storage disease Impaired chemotaxis, bactericidal activity of neutrophils, decreased NK activity	Model for Chediak-Higashi syndrome Crossed onto nude or SCID backgrounds for multiple imune deficiencies
lpr and gld mice	Impaired apoptosis from Fas (lpr) or Fas ligand (gld) defect	Generalized lymphoproliferative disease (gld), autoimmunity, immunodeficiency	Apoptosis studies Autoimmune syndromes
Cytokine KO mice (IL-2, IL-10, IFN-γ, TNF-β, others)	Genetically engineered disruption (knockout) of cytokine gene	Anemia (IL-2), wasting (IL-2, IL-10), and inflammatory bowel disease (IL-2, IL-10) when housed conventionally	Physiological role of cytokines in immune response and inflammation
Receptor KO mice (TcR, Ig, cytokine, MHC, adhesion molecules, integrins)	Genetically engineered disruption (knockout) of receptor gene	Lack functional response to signal of interest, variable immune compromise Inflammatory bowel disease common in TcR KO	Physiological role of receptors in immune response and inflammation