Phenotypes Associated with This Genotype

Genotype
MGI:3628949

• Allelic Composition: Unc13d^Jinx/Unc13d^Jinx
• Genetic Background: C57BL/6J-Unc13d^Jinx/Mmucd

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

immune system

enlarged spleen ( J:119974 )

• 12 days after infection with LCMV, mice have splenomegaly

increased neutrophil cell number ( J:119974 )

• after receiving 2 x 10⁴ PFU MCMV, a 4-fold increase in neutrophil number is observed on day 7 compared to wild-type; this resolves by day 14

• 12 days after infection with LCMV, mice show neutrophilia, rather than neutropenia

increased CD8-positive, alpha-beta T cell number ( J:119974 )

• CD8+ T cells are ~doubled in number in the spleen, after LCMV infection

increased monocyte cell number ( J:119974 )

• after receiving 2 x 10⁴ PFU MCMV, a 3-fold increase in monocyte number is observed on day 7 compared to wild-type; this does not resolve

abnormal NK cell physiology ( J:119974 )

• NK cell-mediated cytotoxicity against beta2microglobulin-null cells in vivo and against YAC-1 cells in vitro is abolished

decreased cytotoxic T cell cytolysis ( J:119974 )

• polyclonal stimulation of CTLs show defect in ability to degranulate

abnormal macrophage physiology ( J:105543 )

• the susceptibility of activated mutant macrophages to ex vivo vesicular stomatitis virus (VSV) infection was reversed by the addition of type I interferon

hemophagocytosis ( J:119974 )

• RBCs are seen to reside within vesicles in bone marrow macrophages

absent lymph node germinal center ( J:119974 )

• germinal center depletion and replacement by macrophages is observed in peripheral lymph nodes after LCMV infection

abnormal cytokine secretion ( J:119974 )

• homozygotes show exaggerated production of Il12, IFNgamma, and type I INF (alpha/beta) 36 hours after inoculation with the virus

• 12 days after infection with LCMV, serum IFNgamma levels show sustained elevation; increased production of IFNgamma by splenic CD8+ T cells is evident

increased susceptibility to Herpesvirales infection ( J:105543 , J:119974 )

• mice are susceptible to infection by mouse cytomegalovirus (MCMV) (J:105543)

• mice are severely ill and have high viral loads in the spleen five days following infection with MCMV (J:105543)

• activated macrophages from these mice are susceptible to ex vivo VSV infection (J:105543)

• when infected with 10⁵ PFU of Smith strain MCMV (mouse cytomegalovirus), mice show severe illness with 4-5 orders of magnitude higher viral titers after 5 days, whereas wild-type C57BL/6 mice survive infection with no signs of illness and very few PFU in the spleen after 5 days (J:119974)

• dose of 2.5 x 10⁵ PFU MCMV is lethal to mutants and BALB/c controls within 6 days while C57BL/6 controls mice do not exhibit any lethality (J:119974)

increased susceptibility to Riboviria infection ( J:105543 , J:119974 )

• activated macrophages from these mice are susceptible to ex vivo VSV infection (J:105543)

• hemophagocytic lymphohistiocytosis (HLH) is observed in mice infected with LCMV (lymphocytic choriomeningitis virus - Armstrong strain) (J:119974)

• infection by LCMV can not be controlled, such that titers are >1000 fold higher in mutants vs controls 12 days after inoculation, except in the liver (J:119974)

hematopoietic system

enlarged spleen ( J:119974 )

• 12 days after infection with LCMV, mice have splenomegaly

anemia ( J:119974 )

• 12 days after infection with LCMV, mice are anemic

increased neutrophil cell number ( J:119974 )

• after receiving 2 x 10⁴ PFU MCMV, a 4-fold increase in neutrophil number is observed on day 7 compared to wild-type; this resolves by day 14

• 12 days after infection with LCMV, mice show neutrophilia, rather than neutropenia

thrombocytopenia ( J:119974 )

• 12 days after infection with LCMV, mice display thrombocytopenia

increased CD8-positive, alpha-beta T cell number ( J:119974 )

• CD8+ T cells are ~doubled in number in the spleen, after LCMV infection

increased monocyte cell number ( J:119974 )

• after receiving 2 x 10⁴ PFU MCMV, a 3-fold increase in monocyte number is observed on day 7 compared to wild-type; this does not resolve

abnormal NK cell physiology ( J:119974 )

• NK cell-mediated cytotoxicity against beta2microglobulin-null cells in vivo and against YAC-1 cells in vitro is abolished

decreased cytotoxic T cell cytolysis ( J:119974 )

• polyclonal stimulation of CTLs show defect in ability to degranulate

abnormal macrophage physiology ( J:105543 )

• the susceptibility of activated mutant macrophages to ex vivo vesicular stomatitis virus (VSV) infection was reversed by the addition of type I interferon

hemophagocytosis ( J:119974 )

• RBCs are seen to reside within vesicles in bone marrow macrophages

skeleton

abnormal bone marrow morphology ( J:119974 )

• bone marrow show macrophage infiltration after LCMV infection; hemophagocytosis can be seen

growth/size/body

enlarged spleen ( J:119974 )

• 12 days after infection with LCMV, mice have splenomegaly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial hemophagocytic lymphohistiocytosis 3		DOID:0110923	OMIM:608898	J:119974