Homozygotes have spherocytic hemolytic anemia and neonatal jaundice. Erythrocytes have diminished biconcavity, a smaller than normal diameter, increased density, an appearance of exovesiculation, and a short lifespan. At birth homozygotes are very pale then become yellow during the first few hours of life and die generally within a day of being born. Although it is rare for a spherocytosis homozygote to survive beyond one day of birth on the WB/Re or C57BL/6J (stock #000450) congenic background, homozygotes on the (C57BL/6J x WB/Re)F1 background are much more robust and the majority survive to adulthood. Those that make it to wean age are expected to have a reasonable lifespan, sometimes living as long as a year. Thus, most studies of this mutation in the adult have been done on the (C57BL/6J x WB/Re)F1 background. These homozygotes display diminished hematocrit, decreased red blood cell count, very elevated red blood cell protoporphyrin levels, increased erythropoiesis, reticulocytosis, hyperbilirubinaemia, cardiomegaly, hepatomegaly, and severe splenomegaly predominantly due to increased red pulp. Large areas of splenic necrosis and fibrosis develop. Thrombi can be found in the atrioventricular valves or within the atria of adults and infarcts have been observed in the myocardium and in the cerebrum, hippocampus, and cerebellum. Iron accumulates in the liver and kidneys, blood urea nitrogen levels become high, and hydronephrosis and membranoproliferative glomerulonephritis are found. By 2 to 3 months of age the urine becomes green due to hemosiderin and ferritin laden renal tubular cells and the urine later becomes red. Kaysser et al. posited that the likely cause of death in adult homozygotes is renal failure.

Development

The spherocytosis mutation arose spontaneously in 1959 at the University of British Columbia Central Animal Depot in the progeny of an unpedigreed stock from Rockland Farms, reported to be C3H. This mutation was imported into The Jackson Laboratory before 1970 and backcrossed onto the C57BL/6J and WB/Re backgrounds by Dr. Elizabeth Russell and Dr. Seldon Bernstein. In 1970 this congenic was at backcross generation N2, in 1976 it reached N9, in 1986 it reached N21 and was subsequently passed into the care of Dr. Jane Barker. In 2010 sperm were cryopreserved from heterozygous males at generation N66.

Selected References

Bernstein SE. 1980. Inherited hemolytic disease in mice: a review and update. Lab Anim Sci 30(2 Pt 1):197-205PubMed: 6763106 MGI: J:162532
JOE M; TEASDALE JM; MILLER JR. 1962. A new mutation (sph) causing neonatal jaundice in the house mouse. Can J Genet Cytol 4:219-25PubMed: 14451913 MGI: J:12276
Kaysser TM; Wandersee NJ; Bronson RT; Barker JE. 1997. Thrombosis and secondary hemochromatosis play major roles in the pathogenesis of jaundiced and spherocytic mice, murine models for hereditary spherocytosis. Blood 90(11):4610-9PubMed: 9373273 MGI: J:44313

View All References

Genetics

Spta1^sph

Allele Symbol: Spta1^sph

Allele Name	spherocytosis
Allele Type	Spontaneous
Allele Synonym(s)	sph
Gene Symbol and Name	Spta1, spectrin alpha, erythrocytic 1
Gene Synonym(s)
Strain of Origin	C3H
Chromosome	1
General Note	This original spherocytosis mutation arose in an unpedigreed C3H stock.
Molecular Note	The mutation in the sph mouse was identified as a single base pair deletion in exon 11 that causes a frame shift and premature stop codon.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

hereditary spherocytosis type 3

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

hereditary spherocytosis type 1

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Spta1^sph related

Hematological Research
- Anemia, Iron Deficiency and Transport Defects
  - hemolytic
- Jaundice
- Hematopoietic Defects
Internal/Organ Research
- Spleen Defects
- Kidney Defects
Cardiovascular Research
- Vascular Defects
  - Thrombosis

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Spta1^sph/Spta1^sph
involves: C3H

cardiovascular system phenotype

enlarged liver sinusoidal spaces

liver vascular congestion
- livers show considerable congestion

homeostasis/metabolism phenotype

increased circulating bilirubin level

integument phenotype

pallor
- extremely pale at birth

liver/biliary system phenotype

abnormal liver morphology
- livers are much darker than in control littermates

enlarged liver

enlarged liver sinusoidal spaces

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

liver vascular congestion
- livers show considerable congestion

mortality/aging

neonatal lethality, complete penetrance
- none survive for more than 24 hours

growth/size/body region phenotype

enlarged liver

hematopoietic system phenotype

abnormal reticulocyte morphology
- reticulocytes do not accumulate alpha spectrin in their membranes and do not synthesize detectable amounts of alpha spectrin

decreased hematocrit

decreased hemoglobin content

hemolytic anemia

poikilocytosis

spherocytosis

Genotype: Spta1^sph/Spta1^sph
either: (B6.C3-Spta1 x WB.C3-Spta1)F1 or (WB.C3-Spta1 x B6.C3-Spta1)F1

growth/size/body region phenotype

enlarged spleen

homeostasis/metabolism phenotype

increased erythrocyte protoporphyrin level
- Percoll-stractan gradients show a considerable increase in erythrocyte density
- red blood cell protoporphyrin levels are about 10 times higher than in controls
- scanning electron microscopy of erythrocytes shows that they have an abnormal shape with disappearance of biconcavity, smaller diameter, and the appearance of exovesiculation

hematopoietic system phenotype

abnormal bone marrow cell number
- CFU-E concentrations in bone marrow are significantly increased over those in wild-type, while BFU-E concentrations are halved
- granuloid:erythroid ratio is 1:3 compared to 3:1 in controls or 1:1 in bled controls

abnormal erythrocyte physiology
- 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

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

abnormal spleen morphology
- 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

decreased hematocrit
- hematocrit average of 15% compared to 45% in controls

enlarged spleen

hemolytic anemia

increased bone marrow cell number
- bone marrow is hypercellular with very high erythrocyte numbers

increased erythrocyte protoporphyrin level
- Percoll-stractan gradients show a considerable increase in erythrocyte density
- red blood cell protoporphyrin levels are about 10 times higher than in controls
- scanning electron microscopy of erythrocytes shows that they have an abnormal shape with disappearance of biconcavity, smaller diameter, and the appearance of exovesiculation

increased erythroid progenitor cell number
- bone marrow contains higher numbers of erythroblasts, proerythroblasts and basophilic erythroblasts

macrocytosis

microcytosis

reticulocytosis

spherocytosis

immune system phenotype

abnormal spleen morphology
- 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

decreased susceptibility to parasitic infection
- homozygotes are resistant to the malarial parasites, Plasmodium chabaudi adami and Plasmodium berghei

enlarged spleen

Genotype: Spta1^sph/Spta1⁺
either: (B6.C3-Spta1 x WB.C3-Spta1)F1 or (WB.C3-Spta1 x B6.C3-Spta1)F1

hematopoietic system phenotype

increased erythrocyte protoporphyrin level
- red blood cells show a higher concentration of protoporphyrin than wild-type

homeostasis/metabolism phenotype

increased erythrocyte protoporphyrin level
- red blood cells show a higher concentration of protoporphyrin than wild-type

Genotype: Spta1^sph/Spta1^sph
(WB.C3-Spta1 x B6.C3-Spta1)F1

cardiovascular system phenotype

cardiac hypertrophy

enlarged heart
- cardiac chambers of surviving adults are dilated

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

hematopoietic system phenotype

abnormal erythrocyte morphology
- 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

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

abnormal erythrocyte physiology
- 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

anisopoikilocytosis

decreased cellular hemoglobin content
- decreased to 16.9% compared to 29.8% in controls

decreased erythrocyte cell number
- adults have very low red blood cell count, 3,740,000/ul instead of 9,150,000/ul

decreased hematocrit
- hematocrit of adults is much lower than normal, 22.5% instead of 45% in controls
- mean hematocrit is reduced to 24.9% from 50.4% in wild-type controls

decreased hemoglobin content
- greatly reduced hemoglobin of 3.7 g/dL compared to 13.5 g/dL in controls
- mean hemoglobin content is reduced to 5.35 g/dl from 15.64 g/dl in wild-type controls

enlarged spleen
- severe splenomegaly with areas of necrosis and fibrosis develops in adults with most of the splenic mass made of red pulp

extramedullary hematopoiesis

hemolysis

hemolytic anemia

increased erythrocyte clearance
- average erythrocyte lifespan of approximately 1 day

increased mean corpuscular volume
- mean MCV raised from 48.1 in wild-type controls to 59.7

increased nucleated erythrocyte cell number
- more than 4 times normal levels

low mean erythrocyte cell number
- less than half of normal numbers

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

poikilocytosis

reticulocytosis
- mean percent of reticulocytes is substantially increased from 3.16% in wild-type controls to 91.2%

schistocytosis

homeostasis/metabolism phenotype

abnormal cardiac thrombosis
- 100% of homozygous adults display cardiac thrombi
- in surviving adults large thrombi are found within the heart mainly in the mitral or left atrioventricular valve

increased circulating bilirubin level

increased kidney iron level
- 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
- 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

cellular phenotype

focal hepatic necrosis

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

renal tubular necrosis

immune system phenotype

enlarged spleen
- severe splenomegaly with areas of necrosis and fibrosis develops in adults with most of the splenic mass made of red pulp

glomerulonephritis

tubular nephritis

liver/biliary system phenotype

enlarged liver

focal hepatic necrosis

increased liver iron level
- 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
- although not jaundiced at birth, homozygotes develop severe jaundice within hours of being born

mortality/aging

postnatal lethality, incomplete penetrance
- 28% die before weaning
- approximately 25% of homozygotes die postnatally

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

muscle phenotype

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

nervous system phenotype

abnormal brain morphology
- infarctions are found in adult cerebrum, hippocampus, and cerebellum, are generally unilateral, and microthrombi are sometimes found close to the infarction

renal/urinary system phenotype

glomerulonephritis

increased kidney iron level
- 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

renal tubular necrosis

tubular nephritis

reproductive system phenotype

infertility

growth/size/body region phenotype

cardiac hypertrophy

decreased body size

enlarged heart
- cardiac chambers of surviving adults are dilated

enlarged liver

enlarged spleen
- severe splenomegaly with areas of necrosis and fibrosis develops in adults with most of the splenic mass made of red pulp

The following phenotype relates to a compound genotype created using this strain

Genotype: Spta1^sph/Spta1^sph
WB.C3-Spta1/BrkJ

mortality/aging

neonatal lethality, incomplete penetrance

postnatal lethality, complete penetrance
- 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

References

Bernstein SE. 1980. Inherited hemolytic disease in mice: a review and update. Lab Anim Sci 30(2 Pt 1):197-205PubMed: 6763106 MGI: J:162532
JOE M; TEASDALE JM; MILLER JR. 1962. A new mutation (sph) causing neonatal jaundice in the house mouse. Can J Genet Cytol 4:219-25PubMed: 14451913 MGI: J:12276
Kaysser TM; Wandersee NJ; Bronson RT; Barker JE. 1997. Thrombosis and secondary hemochromatosis play major roles in the pathogenesis of jaundiced and spherocytic mice, murine models for hereditary spherocytosis. Blood 90(11):4610-9PubMed: 9373273 MGI: J:44313

Additional - Spta1^sph related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the WB-spherocytosis mouse strain in a publication, please cite the originating article(s) and include JAX stock #000454 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Spna1<sph>

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:WB-spherocytosis

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Spta1sph

Allele Symbol: Spta1sph

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Spta1sph related

Mammalian Phenotype Terms by Genotype

Genotype: Spta1sph/Spta1sphinvolves: C3H

cardiovascular system phenotype

homeostasis/metabolism phenotype

integument phenotype

liver/biliary system phenotype

mortality/aging

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Spta1sph/Spta1spheither: (B6.C3-Spta1 x WB.C3-Spta1)F1 or (WB.C3-Spta1 x B6.C3-Spta1)F1

growth/size/body region phenotype

homeostasis/metabolism phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Spta1sph/Spta1+either: (B6.C3-Spta1 x WB.C3-Spta1)F1 or (WB.C3-Spta1 x B6.C3-Spta1)F1

hematopoietic system phenotype

homeostasis/metabolism phenotype

Genotype: Spta1sph/Spta1sph(WB.C3-Spta1 x B6.C3-Spta1)F1

cardiovascular system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

cellular phenotype

immune system phenotype

liver/biliary system phenotype

mortality/aging

muscle phenotype

nervous system phenotype

renal/urinary system phenotype

reproductive system phenotype

growth/size/body region phenotype

Genotype: Spta1sph/Spta1sphWB.C3-Spta1/BrkJ

mortality/aging

References

Additional - Spta1sph related

Genotyping Protocols

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Spta1^sph

Allele Symbol: Spta1^sph

Genotype: Spta1^sph related

Genotype: Spta1^sph/Spta1^sph
involves: C3H

Genotype: Spta1^sph/Spta1^sph
either: (B6.C3-Spta1 x WB.C3-Spta1)F1 or (WB.C3-Spta1 x B6.C3-Spta1)F1

Genotype: Spta1^sph/Spta1⁺
either: (B6.C3-Spta1 x WB.C3-Spta1)F1 or (WB.C3-Spta1 x B6.C3-Spta1)F1

Genotype: Spta1^sph/Spta1^sph
(WB.C3-Spta1 x B6.C3-Spta1)F1

Genotype: Spta1^sph/Spta1^sph
WB.C3-Spta1/BrkJ

Additional - Spta1^sph related