Phenotypes Associated with This Genotype

Genotype
MGI:3688756

• Allelic Composition: Cd74^tm1Liz/Cd74^tm1Liz
• Genetic Background: involves: 129S/SvEv * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

decreased body size ( J:65918 )

• homozygotes are usually smaller than littermates

cachexia ( J:65918 )

• occasionally, homozygotes display symptoms of severe wasting

hematopoietic system

decreased T cell proliferation ( J:72243 )

• immunization with p35-55 does not induce significant T cell proliferation compared to wild-type cells

decreased CD4-positive, alpha-beta T cell number ( J:65918 )

• mutants have decreased numbers of CD4+8- TCRhi T cells in the thymus

• number of CD4+CD8- T cells in the periphery; decreased numbers of mature CD4+ T lymphocytes are seen in analyses of splenic T cells

immune system

decreased T cell proliferation ( J:72243 )

• immunization with p35-55 does not induce significant T cell proliferation compared to wild-type cells

decreased CD4-positive, alpha-beta T cell number ( J:65918 )

• mutants have decreased numbers of CD4+8- TCRhi T cells in the thymus

• number of CD4+CD8- T cells in the periphery; decreased numbers of mature CD4+ T lymphocytes are seen in analyses of splenic T cells

abnormal antigen presentation ( J:72243 )

• splenic antigen presenting cells (APCs) present an encephalitogenic MOG peptide p35-55 to I-A^b-restricted p35-55-specific T cells equivalently to wild-type APCs, stimulating proliferation but are ineffective at presenting intact MOG to T cells compared with wild-type APCs, suggesting that processing is required for presentation of intact MOG

abnormal antigen presentation via MHC class II ( J:65918 )

• mutant spleen cells stimulated stronger responses in presence of already processed peptides hen egg lysozyme (HEL) 74-88 and Ealpha 52-68, but fail to present native protein antigens keyhole limpet cyanin (KLH) and IgG2a

abnormal level of surface class II molecules ( J:65918 )

• mutant spleen cells exhibit reduced levels of I-A^b surface antigen compared to wild-type spleen cells

defective assembly of class II molecules ( J:65918 )

• mutant spleen cells show significantly reduced amounts of alpha/beta heterodimers associated with the invariant chain; increased amounts of free alpha and beta chains are present

• majority of class II molecules are comprised of immature alpha and beta chains that have not been exported past the cis-Golgi

• no mature compact SDS-resistant alpha/beta heterodimers (I-A^b) are produced by mutant spleens in contrast to wild-type cells

• class II molecules produced by mutants show enhanced peptide binding compared to wild-type; molecules behave as if empty or occupied by easily displaced peptide in contrast to wild-type cells that are stably occupied with self and serum-derived peptides

decreased interferon-gamma secretion ( J:72243 )

• immunization with p35-55 does not induce Ifng secretion indicating inability to prime p35-55 specific CD4+ T cells

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:72243 )

• mice do not develop experimental autoimmune encephalitis (EAE) upon direct immunization with p35-55 while wild-type mice do develop EAE

• adoptive transfer of wild-type encephalitogenic T cells does not induce EAE in mutant recipients

cellular

decreased T cell proliferation ( J:72243 )

• immunization with p35-55 does not induce significant T cell proliferation compared to wild-type cells