Phenotypes associated with this allele

• Allele Symbol: Spta1^sph-ha
• Allele Name: hemolytic anemia
• Allele ID: MGI:1856181
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spta1^sph-ha/Spta1^sph-ha	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	MGI:3766996
hm2	Spta1^sph-ha/Spta1^sph-ha	involves: DBA/1J	MGI:2448446
hm3	Spta1^sph-ha/Spta1^sph-ha	(WB.D1-Spta1^sph-ha/Brk x B6.D1-Spta1^sph-ha/Brk)F1	MGI:4437304
ht4	Spta1^sph-ha/Spta1^+	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	MGI:3767060
ht5	Spta1^sph-ha/Spta1^+	involves: DBA/1J	MGI:4819187

Genotype
MGI:3766996

hm1

• 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

increased pulmonary alveolus wall thickness ( 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		J:12830

Genotype
MGI:2448446

hm2

• Allelic Composition: Spta1^sph-ha/Spta1^sph-ha
• Genetic Background: involves: DBA/1J

mortality/aging

postnatal lethality, incomplete penetrance ( J:24729 , J:24829 )

• many animals die within a few days of birth (J:24729)

• Background Sensitivity: most homozygotes die within the first week of life, but some survive to adulthood (J:24829)

prenatal lethality, incomplete penetrance ( J:24829 )

• Background Sensitivity: a small percentage of homozygotes die in utero

pigmentation

abnormal skin pigmentation ( J:14946 )

hematopoietic system

enlarged spleen ( J:14946 , J:30699 )

hemolytic anemia ( J:30699 )

microcytic anemia ( J:24729 )

hypochromic microcytic anemia ( J:14946 )

• severe neonatal hypochromic microcytic anemia

erythroblastosis ( J:14946 )

abnormal erythrocyte morphology ( J:30699 )

• red blood cells are bizzare in shape and staining capacity

decreased hematocrit ( J:24829 )

• newborns have a mean hematocrit of 26.4 compared with 38.8 in controls and adults have a mean hematocrit of 29.1 compared with 48.7 in controls

decreased hemoglobin content ( J:24829 )

• newborns and adults have less than half the normal hemoglobin concentration

decreased mean corpuscular volume ( J:24829 )

• significantly reduced in both newborn homozygotes and adults

microcytosis ( J:24729 )

abnormal reticulocyte morphology ( J:7501 )

• reticulocytes synthesize 6-fold and initially bind 5-fold greater than normal amounts of newly synthesized alpha spectrin, yet accumulate very little in the membrane skeleton

reproductive system

infertility ( J:24729 )

cardiovascular system

cardiac hypertrophy ( J:14946 )

immune system

enlarged spleen ( J:14946 , J:30699 )

liver/biliary system

enlarged liver ( J:30699 )

jaundice ( J:14946 , J:24729 , J:30699 )

skeleton

abnormal bone marrow morphology ( J:30699 )

• bone marrow is hyperplastic

integument

abnormal skin pigmentation ( J:14946 )

growth/size/body

cardiac hypertrophy ( J:14946 )

enlarged liver ( J:30699 )

enlarged spleen ( J:14946 , J:30699 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spherocytosis type 1		DOID:0110916	OMIM:182900	J:14946 , J:30699
hereditary spherocytosis type 3		DOID:0110918	OMIM:270970	J:14946 , J:30699

Genotype
MGI:4437304

hm3

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

mortality/aging

preweaning lethality, incomplete penetrance ( J:162532 )

• approximately 35% die before weaning

hematopoietic system

enlarged spleen ( J:162532 )

extramedullary hematopoiesis ( J:162532 )

hemolytic anemia ( J:162532 )

abnormal erythrocyte morphology ( J:62355 )

• cell surface expression of phosphatidylserine is higher than in wild-type controls, with 11.6% of erythrocytes straining positive for phosphatidylserine versus 1.6% in wild-type controls

low mean erythrocyte cell number ( J:162532 )

• less than half of normal numbers

decreased hematocrit ( J:162532 )

• mean hematocrit is reduced to 26.5% from 50.4% in wild-type controls

decreased hemoglobin content ( J:162532 )

• mean hemoglobin is decreased to 5.52 g/dL compared with 15.64 g/dL in wild-type controls

increased mean corpuscular volume ( J:162532 )

• MCV raised from 48.1 in wil-type controls to 61.6

increased nucleated erythrocyte cell number ( J:162532 )

• more than 3 times normal levels

abnormal red blood cell deformability ( J:81125 )

• red blood cells exhibit a profound decrease in surface area and marked increase in osmotic fragility

anisopoikilocytosis ( J:162532 )

microcytosis ( J:62355 )

• the percentage of erythroid cells that are microcytes is much larger than in wild-type controls

poikilocytosis ( J:162532 )

schistocytosis ( J:162532 )

reticulocytosis ( J:162532 )

• mean percent of reticulocytes is substantially increased from 3.16% in wild-type controls to 93.2%

abnormal erythrocyte physiology ( J:162532 )

• sodium content of erythrocytes is elevated to 55.1 mEq/l from 12.4 mEq/l in wild-type controls, and the membrane cholesterol and phospholipid content is reduced

increased erythrocyte clearance ( J:162532 )

• average erythrocyte lifespan is approximately 1.1 days

hemolysis ( J:162532 )

increased erythrocyte osmotic fragility ( J:162532 )

• increased sensitivity to osmotic lysis

cardiovascular system

cardiac hypertrophy ( J:162532 )

growth/size/body

cardiac hypertrophy ( J:162532 )

decreased body size ( J:162532 )

enlarged liver ( J:162532 )

enlarged spleen ( J:162532 )

homeostasis/metabolism

increased circulating bilirubin level ( J:162532 )

abnormal cardiac thrombosis ( J:62355 )

• 85% of homozygotes display cardiac thrombi

immune system

enlarged spleen ( J:162532 )

liver/biliary system

enlarged liver ( J:162532 )

jaundice ( J:162532 )

• although not jaundiced at birth, homozygotes develop severe jaundice within hours of being born

reproductive system

infertility ( J:162532 )

Genotype
MGI:3767060

ht4

• Allelic Composition: Spta1^sph-ha/Spta1⁺
• 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

hematopoietic system

increased erythrocyte protoporphyrin level ( J:5985 )

• red blood cells show a higher concentration of protoporphyrin than wild-type

homeostasis/metabolism

increased erythrocyte protoporphyrin level ( J:5985 )

• red blood cells show a higher concentration of protoporphyrin than wild-type

Genotype
MGI:4819187

ht5

• Allelic Composition: Spta1^sph-ha/Spta1⁺
• Genetic Background: involves: DBA/1J

hematopoietic system

increased erythrocyte clearance ( J:24829 )

• although erythrocytes are nearly normal in size and hemoglobin concentration, the survival time of erythrocytes in heterozygotes is reduced to 16 days compared with 24 days in controls