Phenotypes Associated with This Genotype

Genotype
MGI:5013951

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Inpp5d^tm1Rav/Inpp5d^tm1Rav; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

• ♀: 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