Phenotypes Associated with This Genotype

Genotype
MGI:3766996

• Allelic Composition: Spta1^sph-ha/Spta1^sph-ha
• Genetic Background: either: (B6.D1-Spta1^sph-ha x WB.D1-Spta1^sph-ha)F1 or (WB.D1-Spta1^sph-ha x B6.D1-Spta1^sph-ha)F1

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

mortality/aging

premature death ( J:12830 )

• 50% of homozygotes die by 6 months of age

hematopoietic system

increased B cell proliferation ( J:1967 )

increased T cell proliferation ( J:1967 )

abnormal erythropoiesis ( J:6695 )

• accelerated erythropoiesis that is associated with distinctive, dark branched cells that make up large portions of the spleen and bone marrow stroma

extramedullary hematopoiesis ( J:12830 )

• extramedullary hematopoiesis in the spleen and liver

hemolytic anemia ( J:1967 , J:6695 , J:12830 )

• chronic hemolytic anemia (J:1967)

abnormal bone marrow cell number ( J:1967 , J:6695 )

• erythroid hyperplasia in the bone marrow (J:1967)

• mean percentage of sIgM+ and B220+ cells is significantly lower in the bone marrow, indicating fewer B lineage lymphocytes in the marrow (J:1967)

• rate of proliferation of large lymphocytes is retarded in the bone marrow (J:1967)

• granuloid:erythroid ratio is 1:2 compared to 3:1 in controls or 1:1 in bled controls (J:6695)

• CFU-E concentrations in bone marrow are significantly increased over those in wild-type, while BFU-E concentrations are halved (J:6695)

increased bone marrow cell number ( J:6695 , J:12830 )

• bone marrow is hypercellular with very high erythrocyte numbers (J:6695)

increased erythroid progenitor cell number ( J:6695 )

• bone marrow contains higher numbers of erythroblasts, proerythroblasts and basophilic erythroblasts

decreased hematocrit ( J:6695 )

• hematocrit average of 21% compared to 45% in controls

increased erythrocyte protoporphyrin level ( J:5985 , J:6695 )

• red blood cell protoporphyrin levels are about 10 times higher than in controls (J:5985)

macrocytosis ( J:6695 )

microcytosis ( J:6695 )

spherocytosis ( J:6695 )

increased leukocyte cell number ( J:12830 )

increased neutrophil cell number ( J:12830 )

increased lymphocyte cell number ( J:1967 , J:12830 )

• significant increase in CD4+, CD8+, and sIgM+ lymphocytes in peripheral blood (J:1967)

• lymphoid expansion is due to redistribution of lymphocytes from the spleen to other peripheral lymphoid tissues as well as increased proliferation of T and B lymphocytes in lymph nodes (J:1967)

increased B cell number ( J:1967 )

• increased numbers of circulating B lymphocytes

increased T cell number ( J:1967 )

• increased numbers of circulating T cells

increased CD4-positive, alpha-beta T cell number ( J:1967 )

increased CD8-positive, alpha-beta T cell number ( J:1967 )

increased monocyte cell number ( J:12830 )

reticulocytosis ( J:6695 )

abnormal spleen morphology ( J:6695 )

• the spleen is extremely erythropoietic and eryhtroclastic, with sheets of erythroblasts associated with dark branching cells alternating with areas filled with macrophages and red cell debris

enlarged spleen ( J:6695 )

abnormal splenic cell ratio ( J:1967 )

• decrease in percentage of lymphocytes in spleen; while control spleens consist of 85-90% lymphocytes, mutants spleens are only about 10-15% lymphocytes

abnormal erythrocyte physiology ( J:30033 )

• erythrocyte intracellular sodium levels are three times higher than normal, erythrocyte intracellular potassium levels are lower than normal, and ouabain induced cation flux rates in erythrocytes are approximately three times higher than normal

increased IgA level ( J:12830 )

• in clinically sick mutants

increased IgG level ( J:12830 )

• in clinically sick mutants

immune system

increased B cell proliferation ( J:1967 )

increased T cell proliferation ( J:1967 )

increased leukocyte cell number ( J:12830 )

increased neutrophil cell number ( J:12830 )

increased lymphocyte cell number ( J:1967 , J:12830 )

• significant increase in CD4+, CD8+, and sIgM+ lymphocytes in peripheral blood (J:1967)

• lymphoid expansion is due to redistribution of lymphocytes from the spleen to other peripheral lymphoid tissues as well as increased proliferation of T and B lymphocytes in lymph nodes (J:1967)

increased B cell number ( J:1967 )

• increased numbers of circulating B lymphocytes

increased T cell number ( J:1967 )

• increased numbers of circulating T cells

increased CD4-positive, alpha-beta T cell number ( J:1967 )

increased CD8-positive, alpha-beta T cell number ( J:1967 )

increased monocyte cell number ( J:12830 )

abnormal spleen morphology ( J:6695 )

• the spleen is extremely erythropoietic and eryhtroclastic, with sheets of erythroblasts associated with dark branching cells alternating with areas filled with macrophages and red cell debris

enlarged spleen ( J:6695 )

abnormal splenic cell ratio ( J:1967 )

• decrease in percentage of lymphocytes in spleen; while control spleens consist of 85-90% lymphocytes, mutants spleens are only about 10-15% lymphocytes

increased IgA level ( J:12830 )

• in clinically sick mutants

increased IgG level ( J:12830 )

• in clinically sick mutants

abnormal lymph node cell ratio ( J:1967 )

• absolute increase in the number of proliferating lymphocytes in the lymph nodes

• mutants have a higher percentage of B cells and lower percentage of T cells in their lymph nodes

lymph node hyperplasia ( J:1967 , J:12830 )

• lymph nodes are 3 times more cellular than wild-type (J:1967)

alveolitis ( J:12830 )

• alveolitis seen in clinically sick mutants

interstitial pneumonia ( J:12830 )

• 18 of 19 clinically sick homozygotes develop actue-to-chronic pneumonitis with variable severity

increased susceptibility to bacterial infection ( J:12830 )

• 45% of clinically sick homozygotes develop bacteremia

cardiovascular system

blood vessel congestion ( J:12830 )

• 18 of 19 clinically sick mutants develop acute vaso-occlusive disease

• 14 of 20 clinically sick homozygotes exhibit myocardial infarction or thrombosis

• 5 of 20 clinically sick homozygotes exhibit splenic infraction

• 8 of 20 clinically sick homozygotes exhibit either liver, bone marrow, pancreas or skeletal muscle infarction

homeostasis/metabolism

increased erythrocyte protoporphyrin level ( J:5985 , J:6695 )

• red blood cell protoporphyrin levels are about 10 times higher than in controls (J:5985)

increased circulating bilirubin level ( J:12830 )

• chronic hyperbillirubinemia is seen in clinically sick mutants

abnormal thrombosis ( J:12830 )

• 80% of homozygotes show evidence of thrombosis in venules and small-to-medium-sized veins, with ischemic tissue damage in one or more organs, including spleen, myocardium, pancreas, and bone marrow

hemosiderosis ( J:12830 )

• renal hemosiderosis is seen in clinically sick homozygotes

liver/biliary system

gallstones ( J:12830 )

• in clinically sick mutants

respiratory system

alveolitis ( J:12830 )

• alveolitis seen in clinically sick mutants

interstitial pneumonia ( J:12830 )

• 18 of 19 clinically sick homozygotes develop actue-to-chronic pneumonitis with variable severity

abnormal lung morphology ( J:12830 )

• 95% of clinically sick homozygotes exhibit lung lesions, ranging from increased cellularity, alveolar wall thickening, exudative pneumonitis and alveolitis, and pulmonary fibrosis

abnormal pulmonary alveolus wall morphology ( J:12830 )

• alveolar wall thickening seen in clinically sick mutants

pulmonary fibrosis ( J:12830 )

• seen in clinically sick mutants

cellular

increased B cell proliferation ( J:1967 )

increased T cell proliferation ( J:1967 )

growth/size/body

enlarged spleen ( J:6695 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sickle cell anemia		DOID:10923	OMIM:603903	J:12830