Phenotypes Associated with This Genotype

Genotype
MGI:7311738

• Allelic Composition: Rarres1^tm1.2Mhl/Rarres1^tm1.2Mhl
• Genetic Background: involves: 129S1/SvImJ * C57BL/6 * FVB/N * NIH Black Swiss

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

neoplasm

increased follicular lymphoma incidence ( J:324270 )

• 77.8% life-time incidence of follicular lymphoma

• lymphoma onset is first detected around 1 year of age

• in some mice, follicular lymphoma shows widespread organ involvement including the liver, mesenteric lymph nodes, inguinal lymph nodes, spleen, pancreas, and cervical lymph nodes

• high grade aggressive follicular lymphoma has characteristics of diffuse large B-cell lymphoma

• however, mice do not show increased incidence of epithelial cancers

immune system

abnormal B cell differentiation ( J:324270 )

• B cells are maintained in a less differentiated state

abnormal plasma cell differentiation ( J:324270 )

• splenic B cells activated in vitro by stimulation with anti-IgM, anti-CD40, and IL-4 (modeling T cell-dependent activation in B cells) show reduced plasma cell differentiation

decreased spleen germinal center number ( J:324270 )

• splenic B cells activated in vitro by stimulation with anti-IgM, anti-CD40, and IL-4 (modeling T cell-dependent activation in B cells) show reduced germinal center B cell formation

abnormal B cell physiology ( J:324270 )

• B cells accumulate at the G0/G1 phase of the cell cycle after 3 days of T cell-dependent activation thus there is an increased number of B cells in G0/G1 and fewer in S and G2/M

• B cells show a small but significant decrease in the levels of NAD+

• however, B cells do not alter mitochondrial oxidative phosphorylation after 24 hours of T cell-dependent activation

decreased B cell apoptosis ( J:324270 )

• resting B cells undergo slightly decreased levels of apoptosis, but the magnitude of protection from apoptosis is not commensurate with the increase in cell viability

abnormal B cell activation ( J:324270 )

• splenic B cells activated in vitro by stimulation with anti-IgM, anti-CD40, and IL-4 (modeling T cell-dependent activation in B cells) show decreased IgG1 production, reduced germinal center B cell formation, and reduced plasma cell differentiation

increased B cell proliferation ( J:324270 )

• resting (unstimulated) B cells are more viable after 3 days in culture while 3-day T cell-dependent activated B cells show only a marginal increase in viability

hematopoietic system

abnormal B cell differentiation ( J:324270 )

• B cells are maintained in a less differentiated state

abnormal plasma cell differentiation ( J:324270 )

• splenic B cells activated in vitro by stimulation with anti-IgM, anti-CD40, and IL-4 (modeling T cell-dependent activation in B cells) show reduced plasma cell differentiation

extramedullary hematopoiesis ( J:324270 )

• mice show survival of CD45+ cells within the liver up to 3 months postnatally suggesting extramedullary hematopoiesis even after birth

• however, mature blood cell and hematopoietic stem progenitor cell (HSPC) numbers are normal, with no changes in T cells and B cells, numbers of macrophages, granulocytes, NK cells, and plasma cells, and normal levels of multipotent progenitor cells and

decreased spleen germinal center number ( J:324270 )

• splenic B cells activated in vitro by stimulation with anti-IgM, anti-CD40, and IL-4 (modeling T cell-dependent activation in B cells) show reduced germinal center B cell formation

abnormal B cell physiology ( J:324270 )

• B cells accumulate at the G0/G1 phase of the cell cycle after 3 days of T cell-dependent activation thus there is an increased number of B cells in G0/G1 and fewer in S and G2/M

• B cells show a small but significant decrease in the levels of NAD+

• however, B cells do not alter mitochondrial oxidative phosphorylation after 24 hours of T cell-dependent activation

decreased B cell apoptosis ( J:324270 )

• resting B cells undergo slightly decreased levels of apoptosis, but the magnitude of protection from apoptosis is not commensurate with the increase in cell viability

abnormal B cell activation ( J:324270 )

• splenic B cells activated in vitro by stimulation with anti-IgM, anti-CD40, and IL-4 (modeling T cell-dependent activation in B cells) show decreased IgG1 production, reduced germinal center B cell formation, and reduced plasma cell differentiation

increased B cell proliferation ( J:324270 )

• resting (unstimulated) B cells are more viable after 3 days in culture while 3-day T cell-dependent activated B cells show only a marginal increase in viability

cellular

abnormal cell physiology ( J:324270 )

• mouse embryonic fibroblasts (MEFs) exhibit increased levels of basal/maximum oxygen consumption, ATP production, and spare respiratory capacity

decreased B cell apoptosis ( J:324270 )

• resting B cells undergo slightly decreased levels of apoptosis, but the magnitude of protection from apoptosis is not commensurate with the increase in cell viability

increased B cell proliferation ( J:324270 )

• resting (unstimulated) B cells are more viable after 3 days in culture while 3-day T cell-dependent activated B cells show only a marginal increase in viability

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
follicular lymphoma		DOID:0050873	OMIM:151430	J:324270