Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bxs6BXSB/MpJ mutation
(0 available);
any
Bxs6 mutation
(0 available)
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
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immune system
 |
• increased levels of gp70 immune complex formation
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• increased gp70 autoantibody titers
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• increased glomerulonephritis incidence and severity
• decreased survival
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hematopoietic system
renal/urinary system
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• increased glomerulonephritis incidence and severity
• decreased survival
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growth/size/body
mortality/aging
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• survival is prolonged compared to mutant mice wild-type for Tlr7
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immune system
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• less severe at 5 months of age compared to mutant mice wild-type for Tlr7
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• activation of splenocytes is reduced compared to mutant mice wild-type for Tlr7
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• autoantibodies show a homogeneous nuclear pattern
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• develop a lupus like syndrome at a later age and in lower numbers compared to mutant mice wild-type for Tlr7
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• increase in anti-RNA IgG levels in the serum at 4 - 6 months of age is less severe than in mutant mice wild-type for Tlr7 and is similar to mice homozygous for Fcgr2btm1Ttk alone
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renal/urinary system
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• kidney disease is less severe at 5 months of age compared to mutant mice wild-type for Tlr7
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hematopoietic system
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• less severe at 5 months of age compared to mutant mice wild-type for Tlr7
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• activation of splenocytes is reduced compared to mutant mice wild-type for Tlr7
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growth/size/body
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• less severe at 5 months of age compared to mutant mice wild-type for Tlr7
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mortality/aging
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• moribund at 5 months of age
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immune system
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• autoantibodies show a nucleolar pattern
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• marked increase in anti-RNA IgG levels in the serum at 4 - 6 months of age
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renal/urinary system
hematopoietic system
growth/size/body
immune system
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• 20% monocytosis incidence in males
• monocytosis incidence is decreased compared to C57BL/6-Nba2NZB Yaa males (71% incidence)
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• increased production of retroviral gp70 immune complex compared to wild-type males
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• 25% incidence of lethal lupus nephritis in males by 14 months of age
• decreased susceptibility to lupus nephritis and decreased glomerular lesion scores compared to C57BL/6-Nba2 Yaa males
• increased glomerular lesion score compared to wild-type males
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renal/urinary system
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• 25% incidence of lethal lupus nephritis in males by 14 months of age
• decreased susceptibility to lupus nephritis and decreased glomerular lesion scores compared to C57BL/6-Nba2 Yaa males
• increased glomerular lesion score compared to wild-type males
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hematopoietic system
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• 20% monocytosis incidence in males
• monocytosis incidence is decreased compared to C57BL/6-Nba2NZB Yaa males (71% incidence)
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hematopoietic system
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N |
• spleen marginal zone B cell numbers are similar to wild-type controls
• splenocyte proliferation in response to imiquimod is similar to controls
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immune system
mortality/aging
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N |
• the hypergammaglobulinemia, autoantibody production, reduced frequencies of marginal zone B cells and monocytosis, renal disease, and premature morbidity that are found in Yaa bearing mice with at least one wildtype copy of the interleukin 21 receptor are ameliorated or prevented by the disruption of the interleukin 21 receptor
(J:144484)
• unlike IL21R heterozygous B2M null controls, these double homozygotes do not develop the Lupus-like autoimmune syndrome caused by Yaa and generally survive beyond 40 weeks of age
(J:179430)
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immune system
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• while BXSB/MpJ males develop SLE-like disease and have a mean survival of 32 weeks, males also homozygous for this null allele of beta-2 microglobulin die much earlier, with a mean survival of only 18 weeks
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• despite the inability to generate serum IgG, there is increased anti-nuclear antibodies in the serum at 14 weeks of age, that is higher than that of BXSB/MpJ males with normal B2M expression
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mortality/aging
immune system
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• while BXSB/MpJ males have a mean survival of 32 weeks before dying from SLE-like syndrome, the additional absence of MHC class I molecules intensifies the severity to a mean survival of only 25 weeks of age
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mortality/aging
immune system
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N |
• due to the absense of alpha/beta T cells these Yaa-bearing males do not develop hypergammaglobulinemia, anti-chromatin auto-antibodies, enlarged lymph nodes or spleen, hemolytic anemia, immune complex glomerulonephritis, monocytosis, or the lupus-like autoimmune disease that normally causes premature death in Yaa-bearing males on the BXSB background, but instead these males are reported to live beyond 300 days
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immune system
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• compared with BXSB/MpJ males that carry Yaa, the additional ablation of CD8A accelerates the mortality from the spontaneous lupus erythematosus-like syndrome such that mortality occurs as early as 12 to 15 weeks of age and mean survival is only 20 weeks of age
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mortality/aging
immune system
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• this null allele diminishes the B cells essential for the Yaa-induced development of Lupus-like autoimmune disease such that these males survive beyond 40 weeks, and do not have the increased splenic populations of CD4+ T cells or CD11b+ monocytes, nor is there elevated ICOS expression in splenic T cells
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immune system
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• while BXSB/MpJ males have a mean survival of 32 weeks before dying from SLE-like syndrome, the additional absence of Tap1 intensifies the severity to a mean survival of only 23 weeks of ag
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mortality/aging
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• disruption of Cd1d1 does not alter the Yaa-induced premature death on this BXSB background, which causes a mean survival of 32 weeks of age in males
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mortality/aging
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• disruption of Fcgrt does not alter the Yaa-induced premature death on this BXSB background, which causes a mean survival of 32 weeks of age in males
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immune system
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• while BXSB/MpJ males develop SLE-like disease and have a mean survival of 32 weeks, males also homozygous for this null allele of beta-2 microglobulin die much earlier, with a mean survival of only approximately 20 weeks
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mortality/aging
immune system
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• death as a result of the Yaa-induced SLE-like autoimmunity is slightly increased in the early segment of the mortality curve relative to Yaa-bearing controls without the null allele
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mortality/aging
mortality/aging
renal/urinary system
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• glomerular deposition of IgG at 14 weeks of age is more severe than that of BXSB/MpJ males
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immune system
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• at 14 weeks of age relative to BSXB/MpJ or BXSB.B6=Yaa+ males
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• scattered follicular distribution in the spleen and large extrafollicular accumulations of CD138+ plasma cells and plasmablasts are found at 14 weeks of age
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• by 14 weeks of age compared with BXSB/MpJ males and the splenocytes have an increased proportion of monocytes, increased ICOS expression on CD4+ T cells, and increased FAS expression on B cells
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• significantly higher than BXSB/MpJ males as early as 4 weeks of age, the earliest timepoint assessed
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• elevated earlier and significantly higher than BXSB/MpJ males as early as 4 weeks of age, the earliest timepoint assessed
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• elevated earlier and significantly higher than BXSB/MpJ males as early as 4 weeks of age, the earliest timepoint assessed
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• while BXSB/MpJ males develop SLE-like disease and have a mean survival of 32 weeks, males homozygous for both null alleles die earlier than those with just one null allele and with a survival curve essentially the same as that of beta 2 microglobulin null Yaa carrying males, with a mean survival of only 18 weeks
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• elevated over BXSB/MpJ males at 6 and 14 weeks of age
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hematopoietic system
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• at 14 weeks of age relative to BSXB/MpJ or BXSB.B6=Yaa+ males
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• scattered follicular distribution in the spleen and large extrafollicular accumulations of CD138+ plasma cells and plasmablasts are found at 14 weeks of age
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• by 14 weeks of age compared with BXSB/MpJ males and the splenocytes have an increased proportion of monocytes, increased ICOS expression on CD4+ T cells, and increased FAS expression on B cells
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• significantly higher than BXSB/MpJ males as early as 4 weeks of age, the earliest timepoint assessed
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• elevated earlier and significantly higher than BXSB/MpJ males as early as 4 weeks of age, the earliest timepoint assessed
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• elevated earlier and significantly higher than BXSB/MpJ males as early as 4 weeks of age, the earliest timepoint assessed
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
ll mutation
(0 available);
any
ll mutation
(0 available)
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
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mortality/aging
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• homozygous males have a mean life span of greater than 21 months, 3 to 4 time longer than non-homozygous males
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endocrine/exocrine glands
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• seen in about 20% of mice
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immune system
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• decrease in CD4+ T cells with age is less pronounced than in non-homozygous males
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• do not develop severe monocytosis, unlike non-homozygous males
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• at 3 to 5 months of age relative to non-homozygous males; however by 2 years of age IgG levels are similar to those in 2 to 3 month old early dying males
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• minimal signs of autoimmune disease are seen at 8 months of age unlike non-homozygous males
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• anti-nuclear antibodies are decreased relative to non-homozygous males
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cardiovascular system
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N |
• no arteritic or degenerative vascular disease or myocardial infarctions are detected
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neoplasm
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• seen in about 20% of mice
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• seen in about 20% of mice
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renal/urinary system
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N |
• glomerular lesions characteristic of aging are seen at 28 months of age but homozygotes do not develop proliferative glomerulonephritis
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hematopoietic system
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• decrease in CD4+ T cells with age is less pronounced than in non-homozygous males
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• do not develop severe monocytosis, unlike non-homozygous males
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• at 3 to 5 months of age relative to non-homozygous males; however by 2 years of age IgG levels are similar to those in 2 to 3 month old early dying males
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immune system
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• CD11b+ monocyte numbers increase as mice age
(J:129409)
• a Gr-1- monocyte subset is the dominant subset by 10 months of age
(J:129409)
• increased susceptibility to monocytosis in males
(J:137656)
• 71% monocytosis incidence in males
(J:137656)
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• increased serum gp70 immune complex levels
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• increased production of serum gp70 immune complex in males
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• increased anti-ribonucleoprotein production in males
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• increased anti-chromatin and anti-DNA antibodies
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• susceptibility to severe glomerulonephritis
(J:95829)
• 50% incidence of lethal lupus nephritis in males by 14 months of age
(J:137656)
• increased lupus nephritis score (severity) in males
(J:137656)
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renal/urinary system
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• susceptibility to severe glomerulonephritis
(J:95829)
• 50% incidence of lethal lupus nephritis in males by 14 months of age
(J:137656)
• increased lupus nephritis score (severity) in males
(J:137656)
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hematopoietic system
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• CD11b+ monocyte numbers increase as mice age
(J:129409)
• a Gr-1- monocyte subset is the dominant subset by 10 months of age
(J:129409)
• increased susceptibility to monocytosis in males
(J:137656)
• 71% monocytosis incidence in males
(J:137656)
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mortality/aging
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• the mean life span of these male mice is 99 days, which is significantly longer than the 88 day mean lifespan that males from this strain normally live
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growth/size/body
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• mice are generally smaller than controls
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immune system
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• increased mast cell numbers are found in the superficial layer of the epidermis, with about a 3-fold increase over controls
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• the characteristic B220+Thy1+ T cells population found in the spleen of mice carrying the Faslps allele is reduced by more than 5-fold in these mice
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hematopoietic system
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• increased mast cell numbers are found in the superficial layer of the epidermis, with about a 3-fold increase over controls
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• the characteristic B220+Thy1+ T cells population found in the spleen of mice carrying the Faslps allele is reduced by more than 5-fold in these mice
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integument
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• pups have scanty growth of short hair on the head and back
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• the number of hair follicles in a given patch of skin appears to be higher than controls but counting is difficult because of the unusual orientation of the follicles
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• axes of hair shafts are randomly oriented, with some being horizontal to the skin layer
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• mice fail to grow vibrissae hairs
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• mice have thick skin with hyperplasia of the epidermis that is prone to injury
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Allelic
Composition |
Fcgr2btm1Ttk/Fcgr2b+
X/Yaa
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Genetic
Background |
involves: 129S4/SvJae * C57BL/6 * SB/Le |
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immune system
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• 58% of mice display monocytosis by 10 months of age with a Gr-1- subset predominating
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hematopoietic system
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• 58% of mice display monocytosis by 10 months of age with a Gr-1- subset predominating
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Allelic
Composition |
Btkm1Anu/Btkm1Anu
X/Yaa
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Genetic
Background |
involves: BXSB/MpJ * C57BL/6JAnu * SB/Le |
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hematopoietic system
immune system
Allelic
Composition |
Fcgr2btm1.2Jsv/Fcgr2b+
X/Yaa
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Genetic
Background |
involves: C57BL/6 * FVB/N * SB/Le |
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mortality/aging
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• mice exhibit greater cumulative death compared with Fcgr2btm1.2Sjv homozygotes
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immune system
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• compared with Fcgr2btm1.2Sjv homozygotes
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• compared with single homozygotes
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• mice develop moderate lupus unlike Fcgr2btm1.2Sjv homozygotes
• however, mice do not develop fatal lupus
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• compared with single homozygotes
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• compared with single homozygotes
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renal/urinary system
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• kidney pathology is increased compared to in Fcgr2btm1.2Sjv homozygotes
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hematopoietic system
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• compared with Fcgr2btm1.2Sjv homozygotes
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• compared with single homozygotes
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growth/size/body
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• compared with Fcgr2btm1.2Sjv homozygotes
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
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|
immune system
|
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• hyperresponsive to imiquimod induced splenocyte proliferation
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hematopoietic system
|
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• hyperresponsive to imiquimod induced splenocyte proliferation
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cellular
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• hyperresponsive to imiquimod induced splenocyte proliferation
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
mortality/aging
|
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• mean longevity for males is 155 +/- 13 days compared to 442 +/- 29 days for littermate females
(J:6235)
• castration does not significantly alter longevity
(J:6235)
• median survival is 8 months
(J:7308)
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immune system
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• 4-fold increase in spleen weight
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• frequency of C3d receptor bearing cells is increased in young mice but declines with age
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• increase in the frequency and absolute numbers of Ig-bearing cells associated with advanced autoimmune disease is seen in males but not females
• frequency of Ig-bearing cells is increased in the thymus
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• at 14 weeks of age, more than normal splenic CD4+ Foxp3+ CD25+ T cells and very few splenic CD8+ Foxp3+ CD25+ T cells and higher than normal expression of CD122 on CD8+ splenic T cells
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• increase in peripheral blood mononuclear cells lacking T and B cells markers is seen by 2 months of age and bemose more severe with age
• at 8 months of age a 16-fold increase in monocytes is seen in males compared to females
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• scattered follicular distribution in the spleen and large extrafollicular accumulations of CD138+ plasma cells and plasmablasts are found at 14 weeks of age
|
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• relative to BXSB.B6-Yaa+ at 14 weeks of age but not at 6 weeks of age
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(J:93740)
(J:179430)
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• relative to BXSB.B6-Yaa+ controls
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• relative to BXSB.B6-Yaa+ controls
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• infiltrated with a mixed population of lymphocytes, plasma cells, and histiocytes often blurring the architecture of the node
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• moderately enlarged
• at 18 to 25 weeks the combined weight of the axillary, mesenteric, and renal lymph nodes is increased 5-fold compared to C57BL/6J males
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• accelerated autoimmune syndrome relative to females of the same strain
(J:6235)
(J:108760)
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• erythrocyte autoantibodies were found in 7 of 13 males between 16 and 25 weeks of age
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• serum anti-nuclear antibodies are found at 6 weeks of age and increased levels at 14 weeks of age
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• acute to subacute exudative and proliferative glomerulonephritis
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hematopoietic system
|
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• 4-fold increase in spleen weight
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• frequency of C3d receptor bearing cells is increased in young mice but declines with age
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• decreased at 16 weeks of age compared to C57BL/6J males
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• increase in the frequency and absolute numbers of Ig-bearing cells associated with advanced autoimmune disease is seen in males but not females
• frequency of Ig-bearing cells is increased in the thymus
|
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• at 14 weeks of age, more than normal splenic CD4+ Foxp3+ CD25+ T cells and very few splenic CD8+ Foxp3+ CD25+ T cells and higher than normal expression of CD122 on CD8+ splenic T cells
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• increase in peripheral blood mononuclear cells lacking T and B cells markers is seen by 2 months of age and bemose more severe with age
• at 8 months of age a 16-fold increase in monocytes is seen in males compared to females
|
|
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• scattered follicular distribution in the spleen and large extrafollicular accumulations of CD138+ plasma cells and plasmablasts are found at 14 weeks of age
|
|
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• relative to BXSB.B6-Yaa+ at 14 weeks of age but not at 6 weeks of age
|
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(J:93740)
(J:179430)
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• relative to BXSB.B6-Yaa+ controls
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• relative to BXSB.B6-Yaa+ controls
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renal/urinary system
|
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• seen at 4 months of age
|
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• acute to subacute exudative and proliferative glomerulonephritis
|
|
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• glomerular depositions of IgG are found at 14 weeks of age
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homeostasis/metabolism
growth/size/body
|
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• 4-fold increase in spleen weight
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
mortality/aging
immune system
|
|
• pronounced decrease in CD4+ T cells with age
|
|
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• accelerated autoimmune syndrome
|
|
|
• anti-nuclear antibody levels are elevated at 3 to 5 months of age
|
|
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• develop severe proliferative glomerulonephritis by 3 to 5 months of age
|
hematopoietic system
|
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• pronounced decrease in CD4+ T cells with age
|
renal/urinary system
|
|
• develop severe proliferative glomerulonephritis by 3 to 5 months of age
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
mortality/aging
|
|
• mean longevity for males is 332 +/- 14 days compared to 716 +/- 28 days for littermate females
|
immune system
|
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• moderately enlarged
• at 18 to 25 weeks the combined weight of the axillary, mesenteric, and renal lymph nodes is increased 5-fold compared to C57BL/6J males
|
|
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• accelerated autoimmune syndrome relative to reciprocal hybrid males
|
Allelic
Composition |
X/Yaa
|
|
Genetic
Background |
involves: BXSB * NZB |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
mortality/aging
|
|
• mean longevity for males is 352 +/- 35 days while males with a wild-type Yaa allele survive 2.5 times longer
|
immune system
|
|
• moderately enlarged
• at 18 to 25 weeks the combined weight of the axillary, mesenteric, and renal lymph nodes is increased 5-fold compared to C57BL/6J males
|
|
|
• accelerated autoimmune syndrome relative to males with a wild-type Yaa allele
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
immune system
|
|
• CD11b+ monocyte numbers increase as mice age with a 3-fold increase by 10 months of age
|
hematopoietic system
|
|
• CD11b+ monocyte numbers increase as mice age with a 3-fold increase by 10 months of age
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
mortality/aging
|
|
• mean longevity for males is 166 +/- 6 days compared to 545 +/- 37 days for reciprocal hybrid males
|
immune system
|
|
• 20-fold increase in spleen weight by 20 weeks of age
|
|
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• infiltrated with a mixed population of lymphocytes, plasma cells, and histiocytes often blurring the architecture of the node
|
|
|
• enlarged 13-fold at 18 to 20 weeks of age compared to reciprocal hybrid males and 6 fold compared to BXSB males
|
|
|
• spleen cell responses to phytohemagglutinin and concanavalin A are reduced and response to E. coli lipopolysaccharide is increased
• however, lymph node cell response to concanavalin A is similar to reciprocal hybrid males
• at 4 weeks of age, in vitro proliferation of spleen cells is increased 3-fold compared to cells from reciprocal hybrid males
|
|
|
• accelerated autoimmune syndrome relative to reciprocal hybrid males
|
|
|
• high titers of thymotoxic autoantibodies were found between 16 and 20 weeks of age in 15 of 16 males
|
|
|
• erythrocyte autoantibodies were found in 16 of 17 males between 16 and 20 weeks of age
|
|
|
• high titers of antinuclear antibody were found between 16 and 20 weeks of age in 14 of 16 males
|
homeostasis/metabolism
hematopoietic system
|
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• 20-fold increase in spleen weight by 20 weeks of age
|
growth/size/body
|
|
• 20-fold increase in spleen weight by 20 weeks of age
|
Allelic
Composition |
X/Yaa
|
|
Genetic
Background |
(NZW x BXSB)F1 |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
mortality/aging
|
|
• 50% mortality is seen at 4.5 months of age compared to 16 months in reciprocal hybrid males
|
immune system
|
|
• gp70 immune complexes are detectable earlier and reach higher concentrations compared to reciprocal hybrid males; however, the total concentration of free and complexed gp70 is similar
|
|
|
• accelerated autoimmune syndrome relative to reciprocal hybrid males
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
mortality/aging
|
|
• 50% and 90% mortality are seen at 4.5 and 8 months of age, respectively, compared to 50% mortality at 15 months in reciprocal hybrid males
|
immune system
|
|
• gp70 immune complexes are detectable earlier and reach higher concentrations compared to reciprocal hybrid males
|
|
|
• accelerated autoimmune syndrome relative to reciprocal hybrid males
|
renal/urinary system
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Yaa mutation
(18 available);
any
Yaa mutation
(21 available)
|
|
|
mortality/aging
|
|
• mean longevity for males is 308 +/- 26 days while only 8 of 16 reciprocal hybrid males died between 270 and 684 days
|
immune system
|
|
• moderately enlarged
• at 18 to 25 weeks the combined weight of the axillary, mesenteric, and renal lymph nodes is increased 5-fold compared to C57BL/6J males
|
|
|
• accelerated autoimmune syndrome relative to reciprocal hybrid males
|
Analysis Tools