Phenotypes Associated with This Genotype

Genotype
MGI:5790974

• Allelic Composition: Procr^tm1.1Pcl/Procr^tm1.1Pcl
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

growth/size/body

enlarged spleen ( J:225914 )

• homozygotes develop severe splenomegaly due to bone marrow failure

increased spleen weight ( J:225914 )

• increased spleen weight at 3 months with a further increase at 1 year of age

mortality/aging

mortality/aging ( J:225914 )

N • homozygotes have a normal lifespan with no evidence of overt pathological thrombosis

homeostasis/metabolism

abnormal circulating protein level ( J:225914 )

• unchallenged homozygotes show a ~40% increase in baseline plasma protein C levels relative to wild-type controls; however, baseline levels of thrombin-antithrombin (TAT) complexes are normal, and no activated protein C (APC) is detectable in healthy homozygotes similar to wild-type controls

• in response to thrombin infusion, plasma APC levels are 8% of those in wild-type controls

• in response to thrombotic challenge with factor Xa/phospholipids (FXa/PCPS), homozygotes show a ~2-fold increase in TAT levels and significantly lower plasma APC levels than wild-type controls

• at 6 hours post-LPS injection, homozygotes show a ~3-fold increase in TAT levels and a ~2-fold decrease in APC levels relative to wild-type controls

increased circulating interleukin-6 level ( J:225914 )

• unchallenged homozygotes show higher plasma IL-6 levels than wild-type controls

• at 2 hours post-LPS injection, homozygotes have significantly higher circulating IL-6 levels than wild-type controls

increased susceptibility to induced thrombosis ( J:225914 )

• in response to thrombotic challenge with FXa/PCPS, homozygotes show increased fibrin deposition in the lungs as well as evidence of large intraventricular fibrin clots in the heart, unlike wild-type controls

hematopoietic system

hematopoietic system phenotype ( J:225914 )

N • homozygotes exhibit normal % of B lymphocytes (B220+), granulocyte progenitors (Gr-1+), megakaryocytes (CD41+), and HSPCs (LSK+) in the bone marrow and spleen and have normal peripheral red and white blood cell counts

enlarged spleen ( J:225914 )

• homozygotes develop severe splenomegaly due to bone marrow failure

increased spleen weight ( J:225914 )

• increased spleen weight at 3 months with a further increase at 1 year of age

extramedullary hematopoiesis ( J:225914 )

• homozygotes show increased extramedullary hematopoiesis as a result of bone marrow failure

decreased bone marrow cell number ( J:225914 )

• homozygotes display decreased total cell numbers in the bone marrow

thrombocytopenia ( J:225914 )

• homozygotes display significantly decreased circulating platelet numbers in peripheral blood relative to wild-type controls

increased spleen red pulp amount ( J:225914 )

• homozygotes show an increased amount of red pulp (90.4% +/- 0.5%) relative to wild-type controls (69.2% +/- 3.03%)

increased splenocyte number ( J:225914 )

• homozygotes show a significant increase in the % of monocytes/macrophages (CD11b+ cells) in spleen

bone marrow failure ( J:225914 )

immune system

enlarged spleen ( J:225914 )

• homozygotes develop severe splenomegaly due to bone marrow failure

increased spleen weight ( J:225914 )

• increased spleen weight at 3 months with a further increase at 1 year of age

increased spleen red pulp amount ( J:225914 )

• homozygotes show an increased amount of red pulp (90.4% +/- 0.5%) relative to wild-type controls (69.2% +/- 3.03%)

increased splenocyte number ( J:225914 )

• homozygotes show a significant increase in the % of monocytes/macrophages (CD11b+ cells) in spleen

bone marrow failure ( J:225914 )

increased circulating interleukin-6 level ( J:225914 )

• unchallenged homozygotes show higher plasma IL-6 levels than wild-type controls

• at 2 hours post-LPS injection, homozygotes have significantly higher circulating IL-6 levels than wild-type controls

increased susceptibility to endotoxin shock ( J:225914 )

• at 2 hours post-LPS injection, homozygotes have significantly higher circulating IL-6 levels than wild-type controls

• at 6 hours post-LPS injection, homozygotes show a ~3-fold increase in TAT complex levels and a ~2-fold decrease in APC levels relative to wild-type controls

• at 24 hours after LPS injection, homozygotes show a significant increase in MPO activity (a marker of neutrophil infiltration) in lung homogenates relative to wild-type controls