All Phenotypes Inpp5d<tm1Rav> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cd79a^tm1(cre)Reth/Cd79a⁺ Inpp5d^tm1Rav/Inpp5d^tm1Rav	involves: 129 * BALB/c * C57BL/6	MGI:6376530
cn2	Inpp5d^tm1Rav/Inpp5d^tm1Rav Cd79a^tm1(cre)Reth/Cd79a⁺ Tg(IghAb36-65)1Wys/0	involves: 129 * BALB/c * C57BL/6 * FVB/N	MGI:6376533
cn3	Cd19^tm1(cre)Cgn/Cd19⁺ Inpp5d^tm1Rav/Inpp5d^tm1Rav Pten^tm1Hwu/Pten^tm1Hwu	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:5013951
cn4	Inpp5d^tm1Rav/Inpp5d^tm1.1Rav Lyz2^tm1(cre)Ifo/Lyz2⁺	involves: 129P2/OlaHsd * C57BL/6	MGI:3716739
cn5	Inpp5d^tm1Rav/Inpp5d^tm1Rav Tg(Cd4-cre)1Cwi/?	involves: C57BL/6 * DBA/2	MGI:3716749

Allelic Composition	Cd79a^tm1(cre)Reth/Cd79a⁺ Inpp5d^tm1Rav/Inpp5d^tm1Rav
Genetic Background	involves: 129 * BALB/c * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd79a^tm1(cre)Reth mutation (3 available); any Cd79a mutation (22 available)
Inpp5d^tm1Rav mutation (1 available); any Inpp5d mutation (93 available)

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

mortality/aging

premature death ( J:178833 )

• mice have a less than 40% survival rate at 1 year

immune system

increased IgG level ( J:178833 )

• IgG deposition in kidney glomeruli is seen at 20 weeks of age

increased susceptibility to systemic lupus erythematosus ( J:178833 )

• mice show autoantibodies that are specifically seen in lupus; ssDNA, dsDNA, dsRNA and chromatin

increased autoantibody level ( J:178833 )

increased anti-nuclear antigen antibody level ( J:178833 )

• anti-nuclear antibodies in the sera in 20-week old mice

increased anti-chromatin antibody level ( J:178833 )

• mice exhibit chromatin autoantibodies at 8 weeks of age and at 20 weeks of age, mice show chromatin antibodies at amounts comparable to those seen in NZB/NZW mice

increased anti-double stranded DNA antibody level ( J:178833 )

increased anti-single stranded DNA antibody level ( J:178833 )

hematopoietic system

increased IgG level ( J:178833 )

• IgG deposition in kidney glomeruli is seen at 20 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:178833

Allelic Composition	Inpp5d^tm1Rav/Inpp5d^tm1Rav Cd79a^tm1(cre)Reth/Cd79a⁺ Tg(IghAb36-65)1Wys/0
Genetic Background	involves: 129 * BALB/c * C57BL/6 * FVB/N

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

immune system

abnormal B cell negative selection ( J:178833 )

• peripheral B cell numbers are reduced by about 70%, suggesting enhanced negative selection

increased plasma cell number ( J:178833 )

• increase in frequency of plasma cells in the B cell population (4.96% of B cells compared to 0.04% in controls)

decreased B cell number ( J:178833 )

• peripheral B cell numbers are reduced by about 70%, suggesting enhanced negative selection

abnormal B cell anergy ( J:178833 )

• cell surface mIgM and mIgD are reduced 50% in B cells and B cells express reduced CD93, CD95, and CD80 indicating a loss of anergic B cells

• B cells lose features of anergy, including antigen unresponsiveness measured by BCR aggregation-induced Akt activation and calcium mobilization

• increase in frequency of B cells with activated phenotype (CD86+)

increased autoantibody level ( J:178833 )

• mice spontaneously express about 4-fold increased autoantibody by 20 weeks of age

hematopoietic system

abnormal B cell negative selection ( J:178833 )

• peripheral B cell numbers are reduced by about 70%, suggesting enhanced negative selection

increased plasma cell number ( J:178833 )

• increase in frequency of plasma cells in the B cell population (4.96% of B cells compared to 0.04% in controls)

decreased B cell number ( J:178833 )

• peripheral B cell numbers are reduced by about 70%, suggesting enhanced negative selection

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

behavior/neurological

lethargy ( J:166155 )

• mutants exhibit lethargy by 4 months of age

hunched posture ( J:166155 )

• mutants exhibit a hunched posture by 4 months of age

growth/size/body

weight loss ( J:166155 )

• mutants exhibit weight loss by 4 months of age

enlarged spleen ( J:166155 )

• mutants exhibit splenomegaly by 4 months of age

hematopoietic system

enlarged spleen ( J:166155 )

• mutants exhibit splenomegaly by 4 months of age

abnormal B cell morphology ( J:166155 )

• CD19+ B cells are larger than B cells from wild-type mice

• B cell neoplasia

decreased B cell number ( J:166155 )

• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse

increased B cell number ( J:166155 )

• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease

abnormal myeloid leukocyte morphology ( J:166155 )

• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells

increased spleen white pulp amount ( J:166155 )

• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp

abnormal B cell physiology ( J:166155 )

• B cells exhibit enhanced survival

increased B cell proliferation ( J:166155 )

• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not

• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

immune system

enlarged spleen ( J:166155 )

• mutants exhibit splenomegaly by 4 months of age

abnormal B cell morphology ( J:166155 )

• B cell neoplasia

• CD19+ B cells are larger than B cells from wild-type mice

decreased B cell number ( J:166155 )

• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse

increased B cell number ( J:166155 )

• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease

abnormal myeloid leukocyte morphology ( J:166155 )

• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells

increased spleen white pulp amount ( J:166155 )

• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp

abnormal B cell physiology ( J:166155 )

• B cells exhibit enhanced survival

increased B cell proliferation ( J:166155 )

• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not

• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

integument

abnormal coat appearance ( J:166155 )

• mutants exhibit ruffled fur by 4 months of age

mortality/aging

premature death ( J:166155 )

• severe morbidity and death occurs in all mutants by 1 year of age

neoplasm

increased lymphoma incidence ( J:166155 )

• mutants develop marginal zone lymphoma, and less frequently, follicular B cell lymphoma or centroblastic lymphoma

increased follicular lymphoma incidence ( J:166155 )

increased splenic marginal zone lymphoma incidence ( J:166155 )

• mutants develop spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma

increased malignant tumor incidence ( J:166155 )

• lymphoma infiltrates are seen in nonlymphoid tissues, including liver, lung, heart, and kidney

increased plasmacytoma incidence ( J:166155 )

cellular

increased B cell proliferation ( J:166155 )

• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not

• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
B-cell lymphoma		DOID:707		J:166155

Allelic Composition	Inpp5d^tm1Rav/Inpp5d^tm1.1Rav Lyz2^tm1(cre)Ifo/Lyz2⁺
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Inpp5d^tm1.1Rav mutation (0 available); any Inpp5d mutation (93 available)
Inpp5d^tm1Rav mutation (1 available); any Inpp5d mutation (93 available)
Lyz2^tm1(cre)Ifo mutation (14 available); any Lyz2 mutation (41 available)

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

hematopoietic system

enlarged spleen ( J:119256 )

• splenomegaly develops at about 5 weeks of age

absent marginal zone B cells ( J:119256 )

• marginal zone B cells are depleted

abnormal spleen marginal zone macrophage morphology ( J:119256 )

• marginal zone macrophages are reorganized

immune system

enlarged spleen ( J:119256 )

• splenomegaly develops at about 5 weeks of age

absent marginal zone B cells ( J:119256 )

• marginal zone B cells are depleted

abnormal spleen marginal zone macrophage morphology ( J:119256 )

• marginal zone macrophages are reorganized

growth/size/body

enlarged spleen ( J:119256 )

• splenomegaly develops at about 5 weeks of age

Allelic Composition	Inpp5d^tm1Rav/Inpp5d^tm1Rav Tg(Cd4-cre)1Cwi/?
Genetic Background	involves: C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Inpp5d^tm1Rav mutation (1 available); any Inpp5d mutation (93 available)
Tg(Cd4-cre)1Cwi mutation (10 available)

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

immune system

abnormal cytotoxic T cell physiology ( J:122796 )

• APC/OVA primed peripheral CD8+ cells have significantly enhanced cytolitic efficiency

abnormal interferon level ( J:122796 )

• under nonpolarizing conditions, IFNgamma levels are higher

abnormal lymph node germinal center morphology ( J:122796 )

• following infection with Alu/NP-CGG, B cell germinal centers are reduced 3-fold

abnormal humoral immune response ( J:122796 )

• following infection with Alu/NP-CGG, Th2 cytokine levels are reduced

abnormal interleukin secretion ( J:122796 )

• following infection with Alu/NP-CGG, lower levels of IL-4, IL-5, and IL-13 are produced

• under nonpolarizing conditions, markedly lower levels of IL-4, IL-5, and IL-13 are produced

decreased susceptibility to parasitic infection ( J:122796 )

• following infection with S. mansoni, mice have smaller granulomas and somewhat reduced levels of eosinophils in the lung and significantly reduced levels of IL-13 Ralpha2 in serum

• in vitro exposure of lymph nodes with ConA or Schistosome egg antigen results in a reduced production of IL4 and IL5 and reduced proliferation of T cells

homeostasis/metabolism

abnormal interferon level ( J:122796 )

• under nonpolarizing conditions, IFNgamma levels are higher

hematopoietic system

abnormal cytotoxic T cell physiology ( J:122796 )

• APC/OVA primed peripheral CD8+ cells have significantly enhanced cytolitic efficiency

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