Mouse Genome Informatics
hm1
    Ccr7tm1Rfor/Ccr7tm1Rfor
B6.129P2(C)-Ccr7tm1Rfor/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice treated with antibiotic to remove commensal bacteria and infected with non-invasive Salmonella exhibit decreased bacterial titers in the mesenteric lymph nodes as compared to wild type controls


Mouse Genome Informatics
hm2
    Ccr7tm1Rfor/Ccr7tm1Rfor
B6.129P2-Ccr7tm1Rfor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• no single positive T cell abnormalities other than the migration defect from cortex to medulla of the thymus (J:93960)
• single positive T cells fail to localize to the medulla of the thymus in newborns (J:93960)
• single positive T cells are retained in the cortex of the thymus (J:93960)
• FTY720-treated mice exhibit an accumulation of mature thymocytes in the cortex rather than medulla of the thymus as in similarly treated wild-type mice (J:110910)
• single positive thymocytes are retained by the cortex rather than migrating to the medulla
• reduced in size in the adult thymus
• medullary volume is about 50% that found in controls
• 18 h after stimulation by fluorescein isothiocyanate skin painting dendritic cells fail to reach the lymph nodes
• this defect can be partially overcome by use of high antigen doses
• mice exhibit autoimmune exocrinopathy unlike wild-type mice
• mice exhibit periductal lymphocyte infiltration in the lacrimal, parotid, and submandibular glands unlike wild-type mice
• parotid and submandicular glands exhibit periductal lymphocyte infiltration unlike in wild-type mice
• mice exhibit sialadenitis unlike wild-type mice
• lacrimal glands exhibit periductal lymphocyte infiltration unlike in wild-type mice
• mice exhibit dacryoadenitis unlike wild-type mice

endocrine/exocrine glands
• parotid and submandicular glands exhibit periductal lymphocyte infiltration unlike in wild-type mice
• mice exhibit sialadenitis unlike wild-type mice
• as early as 5 weeks of age, mice exhibit lesions in exocrine glands unlike wild-type mice
• mice exhibit parotid gland tissue damage associated with inflammation unlike wild-type mice
• mice exhibit submandibular gland tissue damage associated with inflammation unlike wild-type mice
• lacrimal glands exhibit periductal lymphocyte infiltration causing destruction of acinar cells unlike in wild-type mice
• single positive thymocytes are retained by the cortex rather than migrating to the medulla
• reduced in size in the adult thymus
• medullary volume is about 50% that found in controls
• lacrimal glands exhibit periductal lymphocyte infiltration unlike in wild-type mice
• mice exhibit dacryoadenitis unlike wild-type mice

digestive/alimentary system
• mice exhibit parotid gland tissue damage associated with inflammation unlike wild-type mice
• mice exhibit submandibular gland tissue damage associated with inflammation unlike wild-type mice
• parotid and submandicular glands exhibit periductal lymphocyte infiltration unlike in wild-type mice
• mice exhibit sialadenitis unlike wild-type mice

hematopoietic system
• single positive T cells fail to localize to the medulla of the thymus in newborns (J:93960)
• single positive T cells are retained in the cortex of the thymus (J:93960)
• FTY720-treated mice exhibit an accumulation of mature thymocytes in the cortex rather than medulla of the thymus as in similarly treated wild-type mice (J:110910)
• single positive thymocytes are retained by the cortex rather than migrating to the medulla
• medullary volume is about 50% that found in controls
• reduced in size in the adult thymus

homeostasis/metabolism
• FTY720-treated mice exhibit an accumulation of mature thymocytes in the cortex rather than medulla of the thymus as in similarly treated wild-type mice

vision/eye
• lacrimal glands exhibit periductal lymphocyte infiltration causing destruction of acinar cells unlike in wild-type mice
• lacrimal glands exhibit periductal lymphocyte infiltration unlike in wild-type mice
• mice exhibit dacryoadenitis unlike wild-type mice

cellular
• single positive T cells fail to localize to the medulla of the thymus in newborns (J:93960)
• single positive T cells are retained in the cortex of the thymus (J:93960)
• FTY720-treated mice exhibit an accumulation of mature thymocytes in the cortex rather than medulla of the thymus as in similarly treated wild-type mice (J:110910)

Mouse Models of Human Disease
OMIM IDRef(s)
Sjogren Syndrome 270150 J:110910


Mouse Genome Informatics
hm3
    Ccr7tm1Rfor/Ccr7tm1Rfor
involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• dendritic cells transplanted into the footpad fail to drain into lymph nodes unlike wild-type cells


Mouse Genome Informatics
hm4
    Ccr7tm1Rfor/Ccr7tm1Rfor
involves: 129P2/OlaHsd * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• adoptive transfer experiments to wild-type recipients revealed that homozygotes display impaired migration of B cells and T cells into lymph nodes and Peyer's pathces, and of T cells into the splenic periarteriolar lymphoid sheath (PALS)
• unlike wild-type B cells, mutant B cells rapidly leave the outer PALS after being transferred into wild-type recipients
• unlike in wild-type mice, only few, morphologically altered DCs are detected in the T cell zone of mutant lymph nodes
• following FITC skin painting, significantly less skin-derived DCs are found in mutant LNs relative to wild-type controls
• homozygotes show a significant reduction in the percentage of CD62L+ naive T cells in all secondary lymphoid organs relative to wild-type controls
• homozygotes show a significant reduction of CD4+ cell numbers in mesenteric and peripheral lymph nodes (50%-70%) and Peyer's patches (25%) relative to wild-type controls
• homozygotes show a significant expansion of CD62L+ naive T cells in blood and bone marrow relative to wild-type controls
• homozygotes show a 6-fold increase in CD4+ cell numbers in peripheral blood, spleen, and bone marrow relative to wild-type controls
• T cells are mislolocalized and spread throughout the marginal sinuses and the red pulp in large clusters instead of being found in the PALS
• mutant spleens are usually 2- to 3-fold enlarged relative to wild-type spleens
• T cells are mislolocalized and spread throughout the marginal sinuses and the red pulp in large clusters instead of being found in the PALS
• unlike wild-type controls, homozygotes exhibit only very few naive CD62L+ T cells in the T cell zone close to the central artery; those T cells found in PALS are of the memory phenotype lacking CD62L expression
• naive T cells reside outside the PALS in mutant mice
• adoptive transfer experiments revealed that mutant B cells enter the recipients'lymph nodes and Peyer's patches with a frequency of 20%-50% of that observed after transfer of wild-type cells
• unlike wild-type cells, adoptively transferred mutant B cells are not retained in the outer PALS but quickly migrate to the adjacent follicle, suggesting that temporary retention of B cells in this area and interaction with antigen-specifc T cells is perturbed
• homozygotes display improper activation of B cells, as shown by an increased proportion of IgD-IgMlow B cells in the germinal center of lymph nodes
• at 10 weeks of age, mutant B cells isolated from blood and all secondary lymphoid organs express higher levels of MHC II molecules than wild-type B cells
• at 3 weeks of age, homozygotes harbor activated B cells (with increased expression levels of MHC II) only in peripheral lymph nodes but not in blood or spleen
• after immunization with the T cell-dependent antigen DNP-KLH, homozygotes exhibit a significant delay in IgG isotype switching relative to similarly-treated wild-type controls
• adoptive transfer experiments revealed that mutant T cells enter the recipients' lymph nodes and Peyer's patches with a frequency of 5% to 25% of that observed after transfer of wild-type cells
• homozygotes display impaired migration of T cells into the splenic periarteriolar lymphoid sheath (PALS)
• mutant Peyer's patches lack T cell-rich zones
• a small rim of T cells is shown to surround the B cell follicle, not observed in wild-type mice
• mutant Peyer's patches are smaller than wild-type
• homozygotes display an abnormal distribution of B and T cells within the paracortex
• some homozygotes display prominent B cell follicles with significantly enlarged germinal centers in the paracortex
• T cells are abnormally located toward the marginal sinus
• mutant lymph nodes are smaller than wild-type
• following contact sensitization induced by FITC skin painting, homozygotes display impaired migration of activated skin DCs to their draining lumph nodes
• contact hypersensitivity induced by epicutaneous application of FITC in the ear lobe is completely absent, as assessed by ear swelling at 24 and 48 hrs after reexposure of sensitized homozygotes to the same antigen
• delayed type hypersensitivity induced by s.c. injection of KLH in the ear lobe is completely absent, as assessed by ear swelling at 24 and 48 hrs after reexposure of sensitized homozygotes to the same antigen
• following application of the T-dependent antigen DNP-KLH, homozygotes fail to produce specific antibodies of any IgG isotype within the first 10 days

hematopoietic system
• adoptive transfer experiments to wild-type recipients revealed that homozygotes display impaired migration of B cells and T cells into lymph nodes and Peyer's pathces, and of T cells into the splenic periarteriolar lymphoid sheath (PALS)
• unlike wild-type B cells, mutant B cells rapidly leave the outer PALS after being transferred into wild-type recipients
• unlike in wild-type mice, only few, morphologically altered DCs are detected in the T cell zone of mutant lymph nodes
• following FITC skin painting, significantly less skin-derived DCs are found in mutant LNs relative to wild-type controls
• homozygotes show a significant reduction in the percentage of CD62L+ naive T cells in all secondary lymphoid organs relative to wild-type controls
• homozygotes show a significant reduction of CD4+ cell numbers in mesenteric and peripheral lymph nodes (50%-70%) and Peyer's patches (25%) relative to wild-type controls
• homozygotes show a significant expansion of CD62L+ naive T cells in blood and bone marrow relative to wild-type controls
• homozygotes show a 6-fold increase in CD4+ cell numbers in peripheral blood, spleen, and bone marrow relative to wild-type controls
• T cells are mislolocalized and spread throughout the marginal sinuses and the red pulp in large clusters instead of being found in the PALS
• mutant spleens are usually 2- to 3-fold enlarged relative to wild-type spleens
• T cells are mislolocalized and spread throughout the marginal sinuses and the red pulp in large clusters instead of being found in the PALS
• unlike wild-type controls, homozygotes exhibit only very few naive CD62L+ T cells in the T cell zone close to the central artery; those T cells found in PALS are of the memory phenotype lacking CD62L expression
• naive T cells reside outside the PALS in mutant mice
• adoptive transfer experiments revealed that mutant B cells enter the recipients'lymph nodes and Peyer's patches with a frequency of 20%-50% of that observed after transfer of wild-type cells
• unlike wild-type cells, adoptively transferred mutant B cells are not retained in the outer PALS but quickly migrate to the adjacent follicle, suggesting that temporary retention of B cells in this area and interaction with antigen-specifc T cells is perturbed
• homozygotes display improper activation of B cells, as shown by an increased proportion of IgD-IgMlow B cells in the germinal center of lymph nodes
• at 10 weeks of age, mutant B cells isolated from blood and all secondary lymphoid organs express higher levels of MHC II molecules than wild-type B cells
• at 3 weeks of age, homozygotes harbor activated B cells (with increased expression levels of MHC II) only in peripheral lymph nodes but not in blood or spleen
• after immunization with the T cell-dependent antigen DNP-KLH, homozygotes exhibit a significant delay in IgG isotype switching relative to similarly-treated wild-type controls
• adoptive transfer experiments revealed that mutant T cells enter the recipients' lymph nodes and Peyer's patches with a frequency of 5% to 25% of that observed after transfer of wild-type cells
• homozygotes display impaired migration of T cells into the splenic periarteriolar lymphoid sheath (PALS)

cellular
• adoptive transfer experiments to wild-type recipients revealed that homozygotes display impaired migration of B cells and T cells into lymph nodes and Peyer's pathces, and of T cells into the splenic periarteriolar lymphoid sheath (PALS)
• unlike wild-type B cells, mutant B cells rapidly leave the outer PALS after being transferred into wild-type recipients


Mouse Genome Informatics
cx5
    Ccr7tm1Rfor/Ccr7tm1Rfor
Tg(DO11.10)10Dlo/?

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• significantly reduced ability of T regulatory cells to enter mesenteric and peripheral lymph nodes
• more moderately reduced ability of T regulatory cells to enter Peyer's patches and the gut
• greater ability to migrate into the liver
• failure of T regulatory cells to localize to T cell zones of lymph nodes
• reduced movement of T regulatory cells away from peripheral sites of inflammation

cellular

hematopoietic system
• significantly reduced ability of T regulatory cells to enter mesenteric and peripheral lymph nodes
• more moderately reduced ability of T regulatory cells to enter Peyer's patches and the gut
• greater ability to migrate into the liver
• failure of T regulatory cells to localize to T cell zones of lymph nodes
• reduced movement of T regulatory cells away from peripheral sites of inflammation