Phenotypes associated with this allele

• Allele Symbol: Spta1^sph
• Allele Name: spherocytosis
• Allele ID: MGI:1856377
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spta1^sph/Spta1^sph	(WB.C3-Spta1^sph x B6.C3-Spta1^sph)F1	MGI:4819536
hm2	Spta1^sph/Spta1^sph	B6.C3-Spta1^sph/BrkJ	MGI:4819863
hm3	Spta1^sph/Spta1^sph	either: (B6.C3-Spta1^sph x WB.C3-Spta1^sph)F1 or (WB.C3-Spta1^sph x B6.C3-Spta1^sph)F1	MGI:3767061
hm4	Spta1^sph/Spta1^sph	involves: C3H	MGI:2448372
hm5	Spta1^sph/Spta1^sph	WB.C3-Spta1^sph/BrkJ	MGI:4819858
ht6	Spta1^sph/Spta1^+	either: (B6.C3-Spta1^sph x WB.C3-Spta1^sph)F1 or (WB.C3-Spta1^sph x B6.C3-Spta1^sph)F1	MGI:3767062

Genotype
MGI:4819536

hm1

• Allelic Composition: Spta1^sph/Spta1^sph
• Genetic Background: (WB.C3-Spta1^sph x B6.C3-Spta1^sph)F1

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

mortality/aging

premature death ( J:44313 )

• Background Sensitivity: while approximately 75% of homozygotes on this mixed background survive to adulthood, the average lifespan is 5.75 months

postnatal lethality, incomplete penetrance ( J:44313 , J:162532 )

• approximately 25% of homozygotes die postnatally (J:44313)

• 28% die before weaning (J:162532)

cellular

myocardium necrosis ( J:44313 )

• infarcts are found in the myocardium, ventricular or ventricular septal regions, and atrial walls of surviving adult homozygotes

focal hepatic necrosis ( J:44313 )

renal tubular necrosis ( J:44313 )

hematopoietic system

enlarged spleen ( J:44313 , J:162532 )

• severe splenomegaly with areas of necrosis and fibrosis develops in adults with most of the splenic mass made of red pulp (J:44313)

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 13.1% of erythrocytes straining positive for phosphatidylserine versus 1.6% in wild-type controls

decreased erythrocyte cell number ( J:44313 )

• adults have very low red blood cell count, 3,740,000/ul instead of 9,150,000/ul

low mean erythrocyte cell number ( J:162532 )

• less than half of normal numbers

decreased hematocrit ( J:44313 , J:162532 )

• hematocrit of adults is much lower than normal, 22.5% instead of 45% in controls (J:44313)

• mean hematocrit is reduced to 24.9% from 50.4% in wild-type controls (J:162532)

decreased cellular hemoglobin content ( J:44313 )

• decreased to 16.9% compared to 29.8% in controls

decreased hemoglobin content ( J:44313 , J:162532 )

• greatly reduced hemoglobin of 3.7 g/dL compared to 13.5 g/dL in controls (J:44313)

• mean hemoglobin content is reduced to 5.35 g/dl from 15.64 g/dl in wild-type controls (J:162532)

increased mean corpuscular volume ( J:162532 )

• mean MCV raised from 48.1 in wild-type controls to 59.7

increased nucleated erythrocyte cell number ( J:162532 )

• more than 4 times normal levels

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 91.2%

abnormal erythrocyte physiology ( J:162532 )

• sodium content of erythrocytes is elevated to 64.2 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 of approximately 1 day

hemolysis ( J:162532 )

abnormal erythrocyte osmotic lysis ( J:162532 )

• the osmotic fragility curve for erythrocytes shows broader sensitivity to osmotic lysis, with a subpopulation more sensitive and a suppopulation less sensitive

muscle

myocardium necrosis ( J:44313 )

• infarcts are found in the myocardium, ventricular or ventricular septal regions, and atrial walls of surviving adult homozygotes

immune system

enlarged spleen ( J:44313 , J:162532 )

• severe splenomegaly with areas of necrosis and fibrosis develops in adults with most of the splenic mass made of red pulp (J:44313)

glomerulonephritis ( J:44313 )

tubular nephritis ( J:44313 )

homeostasis/metabolism

increased circulating bilirubin level ( J:162532 )

abnormal cardiac thrombosis ( J:44313 , J:62355 )

• in surviving adults large thrombi are found within the heart mainly in the mitral or left atrioventricular valve (J:44313)

• 100% of homozygous adults display cardiac thrombi (J:62355)

increased kidney iron level ( J:44313 )

• extraordinary amounts of iron accumulate in the adult kidney, particularly within the proximal convoluted tubules, leading to green colored urine by 2 to 3 months of age and progressing to hydronephrosis and possible renal failure

increased liver iron level ( J:44313 )

• significant iron stores are found in hepatic cells of the adult, but not in the hematopoietic regions of the liver or in the Kupffer cells

renal/urinary system

renal tubular necrosis ( J:44313 )

increased kidney iron level ( J:44313 )

• extraordinary amounts of iron accumulate in the adult kidney, particularly within the proximal convoluted tubules, leading to green colored urine by 2 to 3 months of age and progressing to hydronephrosis and possible renal failure

glomerulonephritis ( J:44313 )

tubular nephritis ( J:44313 )

liver/biliary system

focal hepatic necrosis ( J:44313 )

enlarged liver ( J:162532 )

increased liver iron level ( J:44313 )

• significant iron stores are found in hepatic cells of the adult, but not in the hematopoietic regions of the liver or in the Kupffer cells

jaundice ( J:162532 )

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

cardiovascular system

myocardium necrosis ( J:44313 )

• infarcts are found in the myocardium, ventricular or ventricular septal regions, and atrial walls of surviving adult homozygotes

enlarged heart ( J:44313 )

• cardiac chambers of surviving adults are dilated

cardiac hypertrophy ( J:162532 )

nervous system

brain lesion ( J:44313 )

• infarctions are found in adult cerebrum, hippocampus, and cerebellum, are generally unilateral, and microthrombi are sometimes found close to the infarction

cerebral infarct ( J:44313 )

growth/size/body

enlarged heart ( J:44313 )

• cardiac chambers of surviving adults are dilated

cardiac hypertrophy ( J:162532 )

decreased body size ( J:162532 )

enlarged liver ( J:162532 )

enlarged spleen ( J:44313 , J:162532 )

• severe splenomegaly with areas of necrosis and fibrosis develops in adults with most of the splenic mass made of red pulp (J:44313)

reproductive system

infertility ( J:162532 )

Genotype
MGI:4819863

hm2

• Allelic Composition: Spta1^sph/Spta1^sph
• Genetic Background: B6.C3-Spta1^sph/BrkJ

mortality/aging

neonatal lethality, incomplete penetrance ( J:162758 )

postnatal lethality, incomplete penetrance ( J:162758 )

• on the inbred WB/Re or C57BL/6J backgrounds homozygotes rarely live to weaning, although a few may, so this mutation is best studied on the F1 hybrid background on which the majority of homozygotes survive to adulthood and some can live to a year or more

Genotype
MGI:3767061

hm3

• Allelic Composition: Spta1^sph/Spta1^sph
• Genetic Background: either: (B6.C3-Spta1^sph x WB.C3-Spta1^sph)F1 or (WB.C3-Spta1^sph x B6.C3-Spta1^sph)F1

hematopoietic system

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

hemolytic anemia ( J:6695 )

abnormal bone marrow cell number ( J:6695 )

• granuloid:erythroid ratio is 1:3 compared to 3:1 in controls or 1:1 in bled controls

• CFU-E concentrations in bone marrow are significantly increased over those in wild-type, while BFU-E concentrations are halved

increased bone marrow cell number ( J:6695 )

• bone marrow is hypercellular with very high erythrocyte numbers

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 15% compared to 45% in controls

increased erythrocyte protoporphyrin level ( J:5985 , J:111131 )

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

• scanning electron microscopy of erythrocytes shows that they have an abnormal shape with disappearance of biconcavity, smaller diameter, and the appearance of exovesiculation (J:111131)

• Percoll-stractan gradients show a considerable increase in erythrocyte density (J:111131)

macrocytosis ( J:6695 )

microcytosis ( J:6695 )

spherocytosis ( J:6695 )

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 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

immune system

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 )

decreased susceptibility to parasitic infection ( J:111131 )

• homozygotes are resistant to the malarial parasites, Plasmodium chabaudi adami and Plasmodium berghei

homeostasis/metabolism

increased erythrocyte protoporphyrin level ( J:5985 , J:111131 )

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

• scanning electron microscopy of erythrocytes shows that they have an abnormal shape with disappearance of biconcavity, smaller diameter, and the appearance of exovesiculation (J:111131)

• Percoll-stractan gradients show a considerable increase in erythrocyte density (J:111131)

growth/size/body

enlarged spleen ( J:6695 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spherocytosis type 3		DOID:0110918	OMIM:270970	J:6695

Genotype
MGI:2448372

hm4

• Allelic Composition: Spta1^sph/Spta1^sph
• Genetic Background: involves: C3H

mortality/aging

neonatal lethality, complete penetrance ( J:12276 )

• none survive for more than 24 hours

hematopoietic system

hemolytic anemia ( J:12276 )

decreased hematocrit ( J:12276 )

decreased hemoglobin content ( J:12276 )

poikilocytosis ( J:12276 )

spherocytosis ( J:12276 )

abnormal reticulocyte morphology ( J:7501 )

• reticulocytes do not accumulate alpha spectrin in their membranes and do not synthesize detectable amounts of alpha spectrin

cardiovascular system

dilated liver sinusoidal space ( J:12276 )

liver vascular congestion ( J:12276 )

• livers show considerable congestion

homeostasis/metabolism

increased circulating bilirubin level ( J:12276 )

liver/biliary system

abnormal liver morphology ( J:12276 )

• livers are much darker than in control littermates

dilated liver sinusoidal space ( J:12276 )

liver vascular congestion ( J:12276 )

• livers show considerable congestion

enlarged liver ( J:12276 )

jaundice ( J:12276 )

• gradually acquire a yellow color during the first few hours of life

integument

pallor ( J:12276 )

• extremely pale at birth

growth/size/body

enlarged liver ( J:12276 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spherocytosis type 1		DOID:0110916	OMIM:182900	J:12276
hereditary spherocytosis type 3		DOID:0110918	OMIM:270970	J:12276

Genotype
MGI:4819858

hm5

• Allelic Composition: Spta1^sph/Spta1^sph
• Genetic Background: WB.C3-Spta1^sph/BrkJ

mortality/aging

neonatal lethality, incomplete penetrance ( J:162758 )

postnatal lethality, complete penetrance ( J:162758 )

• on the inbred WB/Re or C57BL/6J backgrounds homozygotes rarely live to weaning, although a few may, so this mutation is best studied on the F1 hybrid background on which the majority of homozygotes survive to adulthood and some can live to a year or more

Genotype
MGI:3767062

ht6

• Allelic Composition: Spta1^sph/Spta1⁺
• Genetic Background: either: (B6.C3-Spta1^sph x WB.C3-Spta1^sph)F1 or (WB.C3-Spta1^sph x B6.C3-Spta1^sph)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