Mouse Genome Informatics
hm1
    Rassf5tm1Kina/Rassf5tm1Kina
B6.Cg-Rassf5tm1Kina
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• total B and T cells are increased by about 50%
• CD138+B220+ plasma cells are increased in 10 month old female mutants
• total B and T cells are increased by about 50%
• CD44+CD62L- effector-memory T cells are increased in 10 month old female mutants
• lymphocyte hyperproliferation, with lymphocytes exhibiting enhanced S phase entry after stimulation
• primary B cells exhibit accelearated S phase entry after stimulation
• primary T cells exhibit accelerated S phase entry after stimulation
• aged mice exhibit a 2-fold increase in serum IgG compared to wild-type mice
• deposits of IgG and C3 in the kidney
• aged mice exhibit high titers of antibodies to dsDNA
• females exhibit evidence of glomerulonephritis by 10 months of age while males show similar phenotypes at a later age of 15-18 months

tumorigenesis
• mutants develop B220+CD19+ diffuse large B cell lymphomas
• about 30% of mutants develop B cell lymphomas in peripheral lymph nodes and spleen at 1 year of age
• lymphomas are IgM+, IgD+, CD21+, CD23+, and mature B cell type; progressed lymphomas often lose these markers
• lymphomas are monoclonal or oligoclonal in origin
• B cell lymphomas are not related to severity of autoimmune phenotypes
• mutants develop lung adenocarcinomas after 1.5 years of age
• mutants develop hepatocellular carcinomas after 1.5 years of age

hematopoietic system
• total B and T cells are increased by about 50%
• CD138+B220+ plasma cells are increased in 10 month old female mutants
• total B and T cells are increased by about 50%
• CD44+CD62L- effector-memory T cells are increased in 10 month old female mutants
• lymphocyte hyperproliferation, with lymphocytes exhibiting enhanced S phase entry after stimulation
• primary B cells exhibit accelearated S phase entry after stimulation
• primary T cells exhibit accelerated S phase entry after stimulation
• aged mice exhibit a 2-fold increase in serum IgG compared to wild-type mice
• deposits of IgG and C3 in the kidney

homeostasis/metabolism

renal/urinary system
• females exhibit evidence of glomerulonephritis by 10 months of age while males show similar phenotypes at a later age of 15-18 months

Mouse Models of Human Disease
OMIM IDRef(s)
Systemic Lupus Erythematosus; SLE 152700 J:168749


Mouse Genome Informatics
hm2
    Rassf5tm1Kina/Rassf5tm1Kina
involves: C57BL/6 * CBA * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• defective chemokine-triggered lymphocyte adhesion and migration
• decrease in double positive CD4+ CD8+ cells
• increase in single positive CD4+ and CD8+ cells
• cellular migration out of thymus is 10% of wildtype
• boundary of cortex and medulla ambiguous
• spotty appearance of medulla
• total thymocyte numbers decreased 50-60% in 7-9 week old mice
• impairment of B cell maturation
• defective trafficking of B cells into spleen
• increased number of immature B cells in blood
• reciprocal increase in T and B cells in splenic red pulp

immune system
• defective chemokine-triggered lymphocyte adhesion and migration
• decrease in double positive CD4+ CD8+ cells
• increase in single positive CD4+ and CD8+ cells
• cellular migration out of thymus is 10% of wildtype
• boundary of cortex and medulla ambiguous
• spotty appearance of medulla
• total thymocyte numbers decreased 50-60% in 7-9 week old mice
• impairment of B cell maturation
• defective trafficking of B cells into spleen
• increased number of immature B cells in blood
• reciprocal increase in T and B cells in splenic red pulp
• total lymphocyte numbers in peripheral lymph nodes are decreased to one half of wild-type
• decrease in size and cellular density of B cell follicles and T cell zones
• reduced numbers of CD11c+ (Itgax) dendritic cells in spleen
• following activation, dermal and splenic dendritic cells fail to migrate to draining lymph nodes and white pulp

cellular
• defective chemokine-triggered lymphocyte adhesion and migration

endocrine/exocrine glands
• decrease in double positive CD4+ CD8+ cells
• increase in single positive CD4+ and CD8+ cells
• cellular migration out of thymus is 10% of wildtype
• boundary of cortex and medulla ambiguous
• spotty appearance of medulla
• total thymocyte numbers decreased 50-60% in 7-9 week old mice


Mouse Genome Informatics
ht3
    Rassf5tm1Kina/Rassf5+
involves: C57BL/6 * CBA * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• total lymphocyte numbers in peripheral lymph nodes are decreased to one third of wild-type


Mouse Genome Informatics
cx4
    Cdkn1btm2Kin/Cdkn1btm2Kin
Rassf5tm1Kina/Rassf5tm1Kina

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• development of glomerulonephritis that is observed in single Rassf5 homozygotes is suppressed, in addition, CD138+B220+ plasma cells are reduced by 67%, CD44+CD62L- effector-memory T cells are reduced by 28%, and titers of antibodies to dsDNA are decreased by 58% compared to single Rassf5 homozygotes and deposition of IgG in the kidney is rarely detected compared to single Rassf5 homozygotes (J:168749)

homeostasis/metabolism
• incidence of proteinuria is reduced (22%) compared to single Rassf5 homozygotes (63%)

renal/urinary system
• incidence of proteinuria is reduced (22%) compared to single Rassf5 homozygotes (63%)

tumorigenesis
N
• mutants do not develop B cell lymphomas or other tumors (J:168749)