Phenotypes Associated with This Genotype

Genotype
MGI:5445374

• Allelic Composition: Rc3h1^san/Rc3h1⁺
• Genetic Background: involves: C57BL/6JSfdAnu

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

neoplasm

increased T cell derived lymphoma incidence ( J:189087 )

• 36% of heterozygotes show tumors at 4-5 months of age and by 8-15 months of age about 50% of heterozygotes develop T-cell lymphoma

• prevalence of tumors is 1.6 times higher in females (65%) than in males (41%), regardless of age

• affected lymph nodes exhibit effacement of the nodal architecture, prominent vasularization, atypical T cells, and large B cells, features of angioimmunoblastic T-cell lymphoma, however they do not show expanded FDC networks

• clonal rearrangements in the TCR-beta genes are present in tumors

hematopoietic system

increased spleen weight ( J:189087 )

• slight but significant increase in spleen weight; no difference in spleen size is seen between heterozygotes with or without tumors, indicating that splenomegaly does not correlate with lymphadenopathy

increased T follicular helper cell number ( J:189087 )

• non-tumor lymph nodes exhibit an increased frequency of follicular helper T cells compared to wild-type mice

increased IgG level ( J:189087 )

• heterozygotes, both with and without tumors, develop hypergammaglobulinemia, showing a 2- to 3-fold increase in serum IgG levels

• heterozygotes with tumors have a 1.5-fold increase in total serum IgG levels compared to heterozygotes without tumors

abnormal T follicular helper cell physiology ( J:189087 )

• follicular T cells exhibit increased clonality compared with non-follicular T cells from the same lymph node, even in nontumor lymph nodes

immune system

increased spleen weight ( J:189087 )

• slight but significant increase in spleen weight; no difference in spleen size is seen between heterozygotes with or without tumors, indicating that splenomegaly does not correlate with lymphadenopathy

increased T follicular helper cell number ( J:189087 )

• non-tumor lymph nodes exhibit an increased frequency of follicular helper T cells compared to wild-type mice

increased IgG level ( J:189087 )

• heterozygotes, both with and without tumors, develop hypergammaglobulinemia, showing a 2- to 3-fold increase in serum IgG levels

• heterozygotes with tumors have a 1.5-fold increase in total serum IgG levels compared to heterozygotes without tumors

abnormal T follicular helper cell physiology ( J:189087 )

• follicular T cells exhibit increased clonality compared with non-follicular T cells from the same lymph node, even in nontumor lymph nodes

abnormal lymph node morphology ( J:189087 )

• tumor lymph nodes exhibit an increase in the number of macrophages within the paracortex with occasional foci of myeloid metaplasia, dense aggregates of small PAX5+ lymphocytes all over the parenchyma forming follicles without germinal centers, reactive B-blasts and small clusters of mature plasma cells in the interfollicular areas, polymorphic infiltrate composed of small- to medium-sized proliferating CD3+ lymphocytes in the interfollicular compartment, T cells that occasionally form rosettes around large blasts, sinusoidal dilatation, vessels filled with T cells, an increase in the proportion of B cells, an increase in the frequency of myeloid and dendritic cells with monocyte-derived dendritic cells showing a 2- to 3-fold expansion, a decrease in CD8+ dendritic cells, and an increase in proliferation of follicular helper T cells

• nonenlarged lymph nodes from tumor-bearing heterozygotes exhibit preserved nodal architecture, having both primary and secondary follicles with reactive germinal centers as well as an increase of mature plasma cells in the interfollicular area

abnormal lymph node germinal center morphology ( J:189087 )

• germinal centers are hyperplastic in nontumor lymph nodes of heterozygotes with tumors

enlarged lymph nodes ( J:189087 )

• 53% of heterozygotes develop 1 to 4 enlarged lymph nodes, whereas other lymph nodes remain normal

• while some lymph nodes are larger due to tumor development, nontumor lymph nodes in heterozygotes are also often larger than control lymph nodes

growth/size/body

increased spleen weight ( J:189087 )

• slight but significant increase in spleen weight; no difference in spleen size is seen between heterozygotes with or without tumors, indicating that splenomegaly does not correlate with lymphadenopathy

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:189087 )

• 36% of heterozygotes show tumors at 4-5 months of age and by 8-15 months of age about 50% of heterozygotes develop T-cell lymphoma

• prevalence of tumors is 1.6 times higher in females (65%) than in males (41%), regardless of age

• affected lymph nodes exhibit effacement of the nodal architecture, prominent vasularization, atypical T cells, and large B cells, features of angioimmunoblastic T-cell lymphoma, however they do not show expanded FDC networks

• clonal rearrangements in the TCR-beta genes are present in tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
peripheral T-cell lymphoma		DOID:0050749		J:189087