Phenotypes Associated with This Genotype

Genotype
MGI:3818531

• Allelic Composition: Coro1a^ptcd/Coro1a^ptcd
• Genetic Background: B6.CTS-Coro1a^ptcd

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

immune system

increased thymocyte number ( J:141431 )

• the percentage of mature (CD69^loCD62L^hi) single-positive thymocytes is about doubled in these mice

• similar accumulations of mature T cells in the thymus occurs in irradiated wild-type mice reconstituted with mutant bone marrow

abnormal effector T cell morphology ( J:141431 )

• migrating T cells have irregularly shaped protrusions that are often larger in size than controls

decreased CD4-positive, alpha-beta T cell number ( J:141431 )

• CD4⁺ T cell numbers in the periphery are decreased around 10-fold

• even more dramatic reductions are observed in irradiated wild-type mice reconstituted with mutant bone marrow

decreased CD8-positive, alpha-beta T cell number ( J:141431 )

• CD8⁺ T cell numbers in the periphery are decreased around 5-fold

• even more dramatic reductions are observed in irradiated wild-type mice reconstituted with mutant bone marrow

abnormal T cell physiology ( J:141431 )

• in vitro transwell assays demonstrate migration defects in thymic CD4⁺ T cells' response to sphingosine 1-phosphate, CCL21, and CXCL12

• similar defects are observed in the migratory response of CD4⁺CD8⁺ T cells to CXCL12 and of splenic CD4⁺ T cells to CCL21

• mutant T cells co-transferred with wild-type T cells into wild-type hosts are found in lower proportions in lymph nodes indicating a defect in lymph node entry

• mutant T cells have a 3-fold less ability to egress out of a wild-type lymph node over a 20 hour period

• T cells within a lymph node move at a lower median velocity of 6.6 microm/min compared to 9.5 micormeter/minute for wild-type

• T cells within a lymph node also have larger turning angles and less-directed paths than their wild-type counterparts

increased T cell apoptosis ( J:141431 )

• nave CD4⁺ T cells have about 3-fold higher rates of apoptosis in the spleen

abnormal T cell activation ( J:141431 )

• upon CD3 activation, T cells flux less Ca²⁺ than wild-type controls

• however, similar Ca²⁺ flux results as controls are observed when CD4 stimulation is included

hematopoietic system

increased thymocyte number ( J:141431 )

• the percentage of mature (CD69^loCD62L^hi) single-positive thymocytes is about doubled in these mice

• similar accumulations of mature T cells in the thymus occurs in irradiated wild-type mice reconstituted with mutant bone marrow

abnormal effector T cell morphology ( J:141431 )

• migrating T cells have irregularly shaped protrusions that are often larger in size than controls

decreased CD4-positive, alpha-beta T cell number ( J:141431 )

• CD4⁺ T cell numbers in the periphery are decreased around 10-fold

• even more dramatic reductions are observed in irradiated wild-type mice reconstituted with mutant bone marrow

decreased CD8-positive, alpha-beta T cell number ( J:141431 )

• CD8⁺ T cell numbers in the periphery are decreased around 5-fold

• even more dramatic reductions are observed in irradiated wild-type mice reconstituted with mutant bone marrow

abnormal T cell physiology ( J:141431 )

• in vitro transwell assays demonstrate migration defects in thymic CD4⁺ T cells' response to sphingosine 1-phosphate, CCL21, and CXCL12

• similar defects are observed in the migratory response of CD4⁺CD8⁺ T cells to CXCL12 and of splenic CD4⁺ T cells to CCL21

• mutant T cells co-transferred with wild-type T cells into wild-type hosts are found in lower proportions in lymph nodes indicating a defect in lymph node entry

• mutant T cells have a 3-fold less ability to egress out of a wild-type lymph node over a 20 hour period

• T cells within a lymph node move at a lower median velocity of 6.6 microm/min compared to 9.5 micormeter/minute for wild-type

• T cells within a lymph node also have larger turning angles and less-directed paths than their wild-type counterparts

increased T cell apoptosis ( J:141431 )

• nave CD4⁺ T cells have about 3-fold higher rates of apoptosis in the spleen

abnormal T cell activation ( J:141431 )

• upon CD3 activation, T cells flux less Ca²⁺ than wild-type controls

• however, similar Ca²⁺ flux results as controls are observed when CD4 stimulation is included

cellular

increased T cell apoptosis ( J:141431 )

• nave CD4⁺ T cells have about 3-fold higher rates of apoptosis in the spleen

endocrine/exocrine glands

increased thymocyte number ( J:141431 )

• the percentage of mature (CD69^loCD62L^hi) single-positive thymocytes is about doubled in these mice

• similar accumulations of mature T cells in the thymus occurs in irradiated wild-type mice reconstituted with mutant bone marrow

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, Nk cell-positive		DOID:0090014	OMIM:608971	J:141431