Phenotypes Associated with This Genotype

Genotype
MGI:5476653

• Allelic Composition: Stx11^tm1.2Ics/Stx11^tm1.2Ics
• Genetic Background: involves: C57BL/6NTac

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

immune system

decreased NK cell degranulation ( J:193137 )

• in the presence of recombinant IL15 alone or in combination with IL2

decreased leukocyte cell number ( J:193137 )

• in LCMV-infected mice

decreased neutrophil cell number ( J:193137 )

• lack of neutrophilia in LCMV-infected mice

abnormal cytotoxic T cell physiology ( J:193137 )

• impaired degranulation on TCR engagement

• however, activation markers and T cell proliferation are normal, degranulation is rescued by expression of the human protein and CTL priming is normal

decreased cytotoxic T cell cytolysis ( J:193137 )

• reduced killing of anti-CD3-loaded P815 target cells

increased circulating interferon-gamma level ( J:193137 )

• in LCMV-infected mice

increased circulating interleukin-1 beta level ( J:193137 )

• in LCMV-infected mice

increased circulating interleukin-6 level ( J:193137 )

• in LCMV-infected mice

increased circulating tumor necrosis factor level ( J:193137 )

• in LCMV-infected mice

increased susceptibility to Riboviria infection ( J:193137 )

• LCMV-infected mice develop clinical features of hemophagocytic lymphohistiocytosis including weight loss, body temperature drop, hunched posture, lethargy, pancytopenia, lack of neutrophilia, increased circulating aspartate transaminase level, increased circulating lactate dehydrogenase level, increased serum levels of IFN-gamma, IL1b, TNF-alpha and IL6, increased viral load and worsening condition compared with wild-type mice

• LCMV-infected mice develop more severe hemophagocytic lymphohistiocytosis than in Rab27a^ash and Prf1^tm1Sdz homozygotes despite similar viral loads

behavior/neurological

lethargy ( J:193137 )

• in LCMV-infected mice

hunched posture ( J:193137 )

• in LCMV-infected mice

growth/size/body

weight loss ( J:193137 )

• in LCMV-infected mice

homeostasis/metabolism

increased circulating interferon-gamma level ( J:193137 )

• in LCMV-infected mice

increased circulating interleukin-1 beta level ( J:193137 )

• in LCMV-infected mice

increased circulating interleukin-6 level ( J:193137 )

• in LCMV-infected mice

increased circulating tumor necrosis factor level ( J:193137 )

• in LCMV-infected mice

increased circulating aspartate transaminase level ( J:193137 )

• in LCMV-infected mice

increased circulating lactate dehydrogenase level ( J:193137 )

• in LCMV-infected mice

decreased body temperature ( J:193137 )

• in LCMV-infected mice

hematopoietic system

decreased NK cell degranulation ( J:193137 )

• in the presence of recombinant IL15 alone or in combination with IL2

decreased erythrocyte cell number ( J:193137 )

• in LCMV-infected mice

thrombocytopenia ( J:193137 )

• in LCMV-infected mice

decreased leukocyte cell number ( J:193137 )

• in LCMV-infected mice

decreased neutrophil cell number ( J:193137 )

• lack of neutrophilia in LCMV-infected mice

pancytopenia ( J:193137 )

• in LCMV-infected mice

abnormal cytotoxic T cell physiology ( J:193137 )

• impaired degranulation on TCR engagement

• however, activation markers and T cell proliferation are normal, degranulation is rescued by expression of the human protein and CTL priming is normal

decreased cytotoxic T cell cytolysis ( J:193137 )

• reduced killing of anti-CD3-loaded P815 target cells

cellular

decreased NK cell degranulation ( J:193137 )

• in the presence of recombinant IL15 alone or in combination with IL2

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial hemophagocytic lymphohistiocytosis 4		DOID:0110924	OMIM:603552	J:193137