Mouse Genome Informatics
hm
    Jak3tm1Ljb/Jak3tm1Ljb
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
immune system
• large increase in the number of cells classified as myeloid or premonocytic
• lymphopenia is seen in peripheral and bone marrow smears
• at 6-12 months of age, lymphocyte numbers in whole blood suspensions are decreased
• in adult mice, there is about a 20-fold reduction in thymocyte numbers
• at E14 - E15, thymocytes are virtually undetectable
• at E14 only about 200 Thy+ cells are present in the thymus compared to around 20,000 in age-matched heterozygous littermates
• despite the deficit in progenitors, the rate of thymocyte expansion between E14 and E18 and differentiation of thymic progenitors into pro-T cells are similar to that of heterozygous littermates
• at 6-12 months of age, a profound increase in large granular cells is seen in the peripheral blood and spleen
• these large granular cells consist of 2 populations; cells of the neutrophilic lineage and cells of the monocytic lineage
• at 6 - 12 months of age in the bone marrow and spleen
• significantly higher numbers of both segmented and band neutrophils
• the proportion of pro-T cells is increased about 3-fold and fewer cells in transition between pre-T and late pre-T cell stages are found
• both pro-T and pre-T cells have increased CD25 expression
• about a 2-fold increase in apoptotic thymocytes is seen from E14 - E17
• intrathymically injected bone marrow cells show extremely limited ability to reconstitute T cell development especially when in competition with heterozygous or wild-type cells
• most intrathymically injected cells arrest at the CD44+ CD25- double negativeprogenitor cell stage
• from E15 - E17, T cell maturation appears to be delayed by about 1 day compared to age-matched heterozygous littermates
• however, by E18 T cell maturation in homozygous mice has caught up to that of their heterozygous littermates
• CD4+ cells that are present show an activated phenotype (J:56629)
• CD4+ T cells resemble activated or memory T cells (J:128694)
• decrease in thymocyte proliferation in response to CD3 plus CD28 stimulation compared to wild-type
• the proliferative response of splenic T cells in response to T cell receptor plus CD28 stimulation is virtually absent
• increase in the number of myeloid progenitor cells in the peripheral blood and bone marrow
• the general architecture of the spleen is severely disrupted
• may be seen in some mice by as early as 4 months of age
• seen in all mice over 5 months of age
• the white pulp is replaced with a collection of large cells with euchromatic nuclei that are CD3+
• numerous megakaryoctes are present
• increase in the ratio of CD4+ to CD8+ cells
• thymocytes produce less IL12 and IL13 in response to anti-CD3 plus anti-CD28-stimulation compared to wild-type controls
• splenic T cells secrete less IL12 in response to T cell receptor plus CD28 stimulation
• widespread infiltration of the lungs, kidneys, and liver with mononuclear cells

hematopoietic system
• slight decrease in the number of erythroid progenitors in the bone marrow
• large increase in the number of cells classified as myeloid or premonocytic
• lymphopenia is seen in peripheral and bone marrow smears
• at 6-12 months of age, lymphocyte numbers in whole blood suspensions are decreased
• in adult mice, there is about a 20-fold reduction in thymocyte numbers
• at E14 - E15, thymocytes are virtually undetectable
• at E14 only about 200 Thy+ cells are present in the thymus compared to around 20,000 in age-matched heterozygous littermates
• despite the deficit in progenitors, the rate of thymocyte expansion between E14 and E18 and differentiation of thymic progenitors into pro-T cells are similar to that of heterozygous littermates
• at 6-12 months of age, a profound increase in large granular cells is seen in the peripheral blood and spleen
• these large granular cells consist of 2 populations; cells of the neutrophilic lineage and cells of the monocytic lineage
• at 6 - 12 months of age in the bone marrow and spleen
• significantly higher numbers of both segmented and band neutrophils
• the proportion of pro-T cells is increased about 3-fold and fewer cells in transition between pre-T and late pre-T cell stages are found
• both pro-T and pre-T cells have increased CD25 expression
• about a 2-fold increase in apoptotic thymocytes is seen from E14 - E17
• intrathymically injected bone marrow cells show extremely limited ability to reconstitute T cell development especially when in competition with heterozygous or wild-type cells
• most intrathymically injected cells arrest at the CD44+ CD25- double negativeprogenitor cell stage
• from E15 - E17, T cell maturation appears to be delayed by about 1 day compared to age-matched heterozygous littermates
• however, by E18 T cell maturation in homozygous mice has caught up to that of their heterozygous littermates
• CD4+ cells that are present show an activated phenotype (J:56629)
• CD4+ T cells resemble activated or memory T cells (J:128694)
• decrease in thymocyte proliferation in response to CD3 plus CD28 stimulation compared to wild-type
• the proliferative response of splenic T cells in response to T cell receptor plus CD28 stimulation is virtually absent
• increase in the number of myeloid progenitor cells in the peripheral blood and bone marrow
• the general architecture of the spleen is severely disrupted
• may be seen in some mice by as early as 4 months of age
• seen in all mice over 5 months of age
• the white pulp is replaced with a collection of large cells with euchromatic nuclei that are CD3+
• numerous megakaryoctes are present
• increase in the ratio of CD4+ to CD8+ cells
• thymocytes produce less IL12 and IL13 in response to anti-CD3 plus anti-CD28-stimulation compared to wild-type controls
• splenic T cells secrete less IL12 in response to T cell receptor plus CD28 stimulation

Mouse Models of Human Disease
OMIM IDRef(s)
Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Positive 608971 J:64861