Mouse Genome Informatics
hm1
    Lyntm1Ard/Lyntm1Ard
B6.129P2-Lyntm1Ard
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• there is about a doubling in the number of T cells found in the peritoneum
• there is about a doubling in the number of T cells found in the peritoneum
• B cells express lower levels of CD21 and higher levels of CD23 on the cell surface compared to controls
• profound reduction in transitional stage-2 B cells
• about a five-fold reduction in follicular B cells
• profound reduction in marginal zone B cells
• significant expression of MHCII complexes by circulating B cells suggest these B cells are in an activated state
• B cells have enhanced calcium flux upon activation
• myelopoiesis is greatly enhanced in these mice
• there is a significant increase in the number of colonies generated by bone marrow cells or splenocytes in response to in vitro culturing with GM-CSF, M-CSF, or IL-3
• spleen cellularity is reduced by more than half due to B cell lymphopenia
• auto-antibodies of the IgA, IgG IgM classes develop as the mice age
• mice develop anti-DS DNA IgG antibodies as they age with high levels detectable in all mice by 20 weeks of age
• all mice have immunoglobulin complex deposition in the kidney by 8 weeks of age
• 83% of mice also have C3 complement deposition in the kidney
• severe glomerulonephritis occurs in these mice by one year of age

renal/urinary system
• all mice have immunoglobulin complex deposition in the kidney by 8 weeks of age
• 83% of mice also have C3 complement deposition in the kidney
• severe glomerulonephritis occurs in these mice by one year of age

digestive/alimentary system
• there is about a doubling in the number of T cells found in the peritoneum

hematopoietic system
• there is about a doubling in the number of T cells found in the peritoneum
• B cells express lower levels of CD21 and higher levels of CD23 on the cell surface compared to controls
• profound reduction in transitional stage-2 B cells
• about a five-fold reduction in follicular B cells
• profound reduction in marginal zone B cells
• significant expression of MHCII complexes by circulating B cells suggest these B cells are in an activated state
• B cells have enhanced calcium flux upon activation
• myelopoiesis is greatly enhanced in these mice
• there is a significant increase in the number of colonies generated by bone marrow cells or splenocytes in response to in vitro culturing with GM-CSF, M-CSF, or IL-3
• spleen cellularity is reduced by more than half due to B cell lymphopenia


Mouse Genome Informatics
hm2
    Lyntm1Ard/Lyntm1Ard
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• in cervical and inguinal lymph nodes and spleen
• in the peritoneum
• mice exhibit decreased platelet numbers that becomes more pronounced with age (at 6 to 8 weeks in peripheral blood, 1089+/-242 per ul compared to 609+/-207 per ul in wild-type mice; at 52 to 58 weeks in peripheral blood, 2540+/-1050 per ul compared to 1264+/-434 per ul in wild-type mice)
• red and white pulp are often replaced with of red and white pulp with myelomonocytic cells that are often centers of extramedullary hematopoiesis
• myelomonocytic cells often accumulate in other organs and on the surface of the ears, tails and legs
• red and white pulp are often replaced with myelomonocytic cells that are often centers of extramedullary hematopoiesis
• mice develop age-dependent splenomegaly
• 20% of mice greater than 1 year of age exhibit severe splenomegaly with partial to complete replacement of red and white pulp with myelomonocytic cells that are often centers of extramedullary hematopoiesis
• red and white pulp are often replaced with myelomonocytic cells that are often centers of extramedullary hematopoiesis
• basophils show high MHC II expression

immune system
• in cervical and inguinal lymph nodes and spleen
• in the peritoneum
• mice exhibit decreased platelet numbers that becomes more pronounced with age (at 6 to 8 weeks in peripheral blood, 1089+/-242 per ul compared to 609+/-207 per ul in wild-type mice; at 52 to 58 weeks in peripheral blood, 2540+/-1050 per ul compared to 1264+/-434 per ul in wild-type mice)
• red and white pulp are often replaced with myelomonocytic cells that are often centers of extramedullary hematopoiesis
• mice develop age-dependent splenomegaly
• 20% of mice greater than 1 year of age exhibit severe splenomegaly with partial to complete replacement of red and white pulp with myelomonocytic cells that are often centers of extramedullary hematopoiesis
• red and white pulp are often replaced with myelomonocytic cells that are often centers of extramedullary hematopoiesis
• basophils show high MHC II expression
• increased circulating immune complexes reactive to complement component 1 q

homeostasis/metabolism
• increased circulating immune complexes reactive to complement component 1 q
• elevated albumin-to-creatinine ratio

renal/urinary system
• elevated albumin-to-creatinine ratio

Mouse Models of Human Disease
OMIM IDRef(s)
Systemic Lupus Erythematosus; SLE 152700 J:161523


Mouse Genome Informatics
cx3
    Blktm1Tara/Blktm1Tara
Fyntm1Sor/Fyntm1Sor
Lyntm1Ard/Lyntm1Ard

either: B6.129-Lyntm1Ard Fyntm1Sor Blktm1Tara or (involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• impaired development of B cells results in severe B cell lymphopenia characterized by a decrease in B cell numbers in the spleen, lymph nodes, and peritoneal cavity to 1/60-1/100 of wild-type
• mutant bone marrow is unable to reconstitute B cell development when transferred into lethally irradiated C57BL/6 mice
• exhibit a decrease in immature and B cells in the bone marrow
• exhibit a reduction in the fraction of viable B220+CD43-IgM- pre-B cells to 10% of wild-type
• 3-fold increase in frequency of apoptotic pre-B cells
• pro-B cells exhibit impaired anti-Igbeta-induced NF-kappaB activation
• block in early B cell development

hematopoietic system
• impaired development of B cells results in severe B cell lymphopenia characterized by a decrease in B cell numbers in the spleen, lymph nodes, and peritoneal cavity to 1/60-1/100 of wild-type
• mutant bone marrow is unable to reconstitute B cell development when transferred into lethally irradiated C57BL/6 mice
• exhibit a decrease in immature and B cells in the bone marrow
• exhibit a reduction in the fraction of viable B220+CD43-IgM- pre-B cells to 10% of wild-type
• 3-fold increase in frequency of apoptotic pre-B cells
• pro-B cells exhibit impaired anti-Igbeta-induced NF-kappaB activation
• block in early B cell development


Mouse Genome Informatics
cx4
    KitW-sh/KitW-sh
Lyntm1Ard/Lyntm1Ard

involves: 101 * 129P2/OlaHsd * C3H/HeH
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• in the bone marrow, blood and spleen

immune system
• in the bone marrow, blood and spleen
• increased circulating immune complexes reactive to complement component 1 q

homeostasis/metabolism
• increased circulating immune complexes reactive to complement component 1 q
• elevated albumin-to-creatinine ratio

renal/urinary system
• elevated albumin-to-creatinine ratio

Mouse Models of Human Disease
OMIM IDRef(s)
Systemic Lupus Erythematosus; SLE 152700 J:161523


Mouse Genome Informatics
cx5
    Il4tm1Kopf/Il4tm1Kopf
Lyntm1Ard/Lyntm1Ard

involves: 129P2/OlaHsd * 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• in the bone marrow, blood and spleen
• in the peritoneum

immune system
• in the bone marrow, blood and spleen
• in the peritoneum
• increased circulating immune complexes reactive to complement component 1 q
• yet decreased compared to Lyn single mutant
• yet decreased compared to Lyn single mutant

homeostasis/metabolism
• increased circulating immune complexes reactive to complement component 1 q


Mouse Genome Informatics
cx6
    Igh-7tm1Led/Igh-7tm1Led
Lyntm1Ard/Lyntm1Ard

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• in the bone marrow, blood and spleen

immune system
• in the bone marrow, blood and spleen
• increased circulating immune complexes reactive to complement component 1 q
• yet decreased compared to Lyn single mutant
• yet decreased compared to Lyn single mutant

homeostasis/metabolism
• increased circulating immune complexes reactive to complement component 1 q


Mouse Genome Informatics
cx7
    Lyntm1Ard/Lyntm1Ard
Tg(IghelMD4)4Ccg/0

involves: 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
• B cells have altered kinetics of calcium fluxing upon BCR engagement with delayed influx but an ultimately higher peak intracellular concentration
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is blocked at the immature B cell stage instead of anergy inducation in mature B cells as occurs with wild-type bone marrow
• mature B cells have 4-5 lower sIgM levels on their surface
• B1 B cells are absent in these mice
• hypersecretion of the transgenic IgM antibody occurs in these mice

hematopoietic system
• B cells have altered kinetics of calcium fluxing upon BCR engagement with delayed influx but an ultimately higher peak intracellular concentration
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is blocked at the immature B cell stage instead of anergy inducation in mature B cells as occurs with wild-type bone marrow
• mature B cells have 4-5 lower sIgM levels on their surface
• B1 B cells are absent in these mice
• hypersecretion of the transgenic IgM antibody occurs in these mice


Mouse Genome Informatics
cx8
    Lyntm1Ard/Lyn+
Tg(IghelMD4)4Ccg/0

involves: 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
• mature B cells have about 2-fold lower surface IgM levels

hematopoietic system
• mature B cells have about 2-fold lower surface IgM levels


Mouse Genome Informatics
cx9
    Lyntm1Ard/Lyn+
Ptpn6me-v/Ptpn6+
Tg(IghelMD4)4Ccg/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• mature B cells have about 4-fold lower surface IgM levels

immune system
• mature B cells have about 4-fold lower surface IgM levels


Mouse Genome Informatics
cx10
    Cd22tm1Eac/Cd22+
Lyntm1Ard/Lyn+
Ptpn6me-v/Ptpn6+
Tg(IghelMD4)4Ccg/0

involves: 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
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is almost completely blocked at the immature B cell stage
• surface expression of IgM is only 15% of controls
• half the mice have a 15-fold increase in Hel-specific serum IgM

hematopoietic system
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is almost completely blocked at the immature B cell stage
• surface expression of IgM is only 15% of controls
• half the mice have a 15-fold increase in Hel-specific serum IgM


Mouse Genome Informatics
cx11
    Cd22tm1Eac/Cd22+
Lyntm1Ard/Lyn+
Tg(IghelMD4)4Ccg/0

involves: 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
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is patially blocked at the immature B cell stage
• surface expression of IgM is less than half of controls

hematopoietic system
• when mutant bone marrow is transferred to mice expressing hen egg lysozyme, B cell maturation is patially blocked at the immature B cell stage
• surface expression of IgM is less than half of controls