Overview

Also Known As: WB-hemolytic anemia

These mice carry a spontaneous mutation at the Spta1 locus characterized by spherocytosis and some aspects of sickle cell anemia.

Genetic overview

Genetic Background	Generation

Spta1^sph-ha

Allele Type	Gene Symbol	Gene Name
Spontaneous	Spta1	spectrin alpha, erythrocytic 1

View Genetics

Research Applications

Hematological Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Homozygotes provide a molecular and phenotypic model of hereditary spherocytosis type 3 and a phenotypic model for hereditary spherocytosis type 1 and some aspects of sickle cell anemia. Most phenotypic assessment has been performed using F1 homozygous offspring of heterozygotes from the C57BL/6J and WB/Re congenic strains or homozygotes generated on a B6;WB segregating background. Approximately half die by 6 months of age. Homozygotes display hemolytic anemia with spherocytosis, microcytosis, reduced hematocrit, reticulocytisis, extramedullary hematopoiesis in the spleen and liver, lymphocytosis, neutrophilia, lymph node hyperlasia, and cardiac hypertrophy. Homozygotes can be identified within the first day of birth by their jaundiced color. Consequent to the underlying disorder, homozygotes are prone to developing gallstones, pneumonitis, and vaso-occulsive disease in multiple organs.

Development

The hymolytic anemia mutation arose spontaneously in the DBA/1J inbred strain at The Jackson Laboratory in approximately 1960. This mutation was backcrossed onto the C57BL/6J and WB/Re inbred backgrounds by Seldon Bernstein. The WB/Re congenic reached generation N5 in 1968, N9 in 1970, N24 in 1978, N34 in 1986 and was subsequently transferred to the colony of Dr. Jane Barker. In 2010 sperm were cryopreserved from heterozygous males at generation N81.

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

View All References

Genetics

Spta1^sph-ha

Allele Symbol: Spta1^sph-ha

Allele Name	hemolytic anemia
Allele Type	Spontaneous
Allele Synonym(s)	hemolytic anemia; Spta1^sph-ha
Gene Symbol and Name	Spta1, spectrin alpha, erythrocytic 1
Gene Synonym(s)	ha; expressed sequence AF093576; sph; ihj; Spna-1; HPP; Spna1; ihj; Spna1; SPTA; iasi hereditary jaundice; Spna-1; SPH3; HS3; EL2; erythroid; hemolytic anemia; expressed sequence AI451697; spectrin alpha 1; spherocytosis; AF093576; AI451697
Strain of Origin	DBA/1J
Chromosome	1
Molecular Note	The mutation in the sph-ha mouse (also known as sph-J) was identified as a C to A transversion in exon 52 that converts a tyrosine to a stop codon. This mutation truncates the protein by 13 amino acids.

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).

Research Areas By Genotype

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

Genotype: Spta1^sph-ha related

Hematological Research
- Anemia, Iron Deficiency and Transport Defects
  - hypochromic anemia
  - microcytic
  - hemolytic
- Jaundice
- Hematopoietic Defects
Developmental Biology Research
- Postnatal Lethality
  - Homozygous

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-ha/Spta1^sph-ha
involves: DBA/1J

cardiovascular system phenotype

cardiac hypertrophy

immune system phenotype

enlarged spleen

integument phenotype

abnormal skin pigmentation

liver/biliary system phenotype

enlarged liver

jaundice

hematopoietic system phenotype

abnormal erythrocyte morphology
- red blood cells are bizzare in shape and staining capacity

abnormal reticulocyte morphology
- 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

decreased hematocrit
- 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
- newborns and adults have less than half the normal hemoglobin concentration

decreased mean corpuscular volume
- significantly reduced in both newborn homozygotes and adults

enlarged spleen

erythroblastosis

hemolytic anemia

hypochromic microcytic anemia
- severe neonatal hypochromic microcytic anemia

microcytic anemia

microcytosis

mortality/aging

postnatal lethality, incomplete penetrance
- many animals die within a few days of birth
- Background Sensitivity - most homozygotes die within the first week of life, but some survive to adulthood

prenatal lethality, incomplete penetrance
- Background Sensitivity - a small percentage of homozygotes die in utero

pigmentation phenotype

abnormal skin pigmentation

reproductive system phenotype

infertility

skeleton phenotype

abnormal bone marrow morphology
- bone marrow is hyperplastic

Genotype: Spta1^sph-ha/Spta1^sph-ha
either:(B6.D1-Spta1 x WB.D1-Spta1)F1 or (WB.D1-Spta1 x B6.D1-Spta1)F1

cardiovascular system phenotype

vasculature congestion
- 14 of 20 clinically sick homozygotes exhibit myocardial infarction or thrombosis
- 18 of 19 clinically sick mutants develop acute vaso-occlusive disease
- 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 phenotype

abnormal thrombosis
- 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
- renal hemosiderosis is seen in clinically sick homozygotes

increased circulating bilirubin level
- chronic hyperbillirubinemia is seen in clinically sick mutants

increased erythrocyte protoporphyrin level
- red blood cell protoporphyrin levels are about 10 times higher than in controls

cellular phenotype

increased B cell proliferation

increased T cell proliferation

immune system phenotype

abnormal lymph node cell ratio
- 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

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

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

alveolitis
- alveolitis seen in clinically sick mutants

enlarged spleen

increased B cell number
- increased numbers of circulating B lymphocytes

increased B cell proliferation

increased CD4-positive, alpha beta T cell number

increased CD8-positive, alpha-beta T cell number

increased IgA level
- in clinically sick mutants

increased IgG level
- in clinically sick mutants

increased leukocyte cell number

increased lymphocyte cell number
- 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
- significant increase in CD4+, CD8+, and sIgM+ lymphocytes in peripheral blood

increased monocyte cell number

increased neutrophil cell number

increased susceptibility to bacterial infection
- 45% of clinically sick homozygotes develop bacteremia

increased T cell number
- increased numbers of circulating T cells

increased T cell proliferation

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

lymph node hyperplasia
- lymph nodes are 3 times more cellular than wild-type

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
- erythroid hyperplasia in the bone marrow
- granuloid:erythroid ratio is 1:2 compared to 3:1 in controls or 1:1 in bled controls
- mean percentage of sIgM+ and B220+ cells is significantly lower in the bone marrow, indicating fewer B lineage lymphocytes in the marrow
- rate of proliferation of large lymphocytes is retarded in the bone marrow

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

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

decreased hematocrit
- hematocrit average of 21% compared to 45% in controls

enlarged spleen

extramedullary hematopoiesis
- extramedullary hematopoiesis in the spleen and liver

hemolytic anemia
- chronic hemolytic anemia

increased B cell number
- increased numbers of circulating B lymphocytes

increased B cell proliferation

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

increased CD4-positive, alpha beta T cell number

increased CD8-positive, alpha-beta T cell number

increased erythrocyte protoporphyrin level
- red blood cell protoporphyrin levels are about 10 times higher than in controls

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

increased IgA level
- in clinically sick mutants

increased IgG level
- in clinically sick mutants

increased leukocyte cell number

increased lymphocyte cell number
- 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
- significant increase in CD4+, CD8+, and sIgM+ lymphocytes in peripheral blood

increased monocyte cell number

increased neutrophil cell number

increased T cell number
- increased numbers of circulating T cells

increased T cell proliferation

macrocytosis

microcytosis

reticulocytosis

spherocytosis

liver/biliary system phenotype

gallstones
- in clinically sick mutants

mortality/aging

premature death
- 50% of homozygotes die by 6 months of age

respiratory system phenotype

abnormal lung morphology
- 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
- alveolar wall thickening seen in clinically sick mutants

alveolitis
- alveolitis seen in clinically sick mutants

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

pulmonary fibrosis
- seen in clinically sick mutants

Genotype: Spta1^sph-ha/Spta1⁺
either:(B6.D1-Spta1 x WB.D1-Spta1)F1 or (WB.D1-Spta1 x B6.D1-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-ha/Spta1^sph-ha
(WB.D1-Spta1/Brk x B6.D1-Spta1/Brk)F1

cardiovascular system phenotype

cardiac hypertrophy

growth/size/body region phenotype

decreased body size

homeostasis/metabolism phenotype

abnormal thrombosis
- 85% of homozygotes display cardiac thrombi

increased circulating bilirubin level

immune system phenotype

enlarged spleen

liver/biliary system phenotype

enlarged liver

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

mortality/aging

preweaning lethality, incomplete penetrance
- approximately 35% die before weaning

reproductive system phenotype

infertility

hematopoietic system phenotype

abnormal erythrocyte morphology
- 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

abnormal erythrocyte osmotic lysis
- increased sensitivity to osmotic lysis

abnormal erythrocyte physiology
- 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

abnormal red blood cell deformability
- red blood cells exhibit a profound decrease in surface area and marked increase in osmotic fragility

anisopoikilocytosis

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

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

enlarged spleen

extramedullary hematopoiesis

hemolysis

hemolytic anemia

increased erythrocyte clearance
- average erythrocyte lifespan is approximately 1.1 days

increased mean corpuscular volume
- MCV raised from 48.1 in wil-type controls to 61.6

increased nucleated erythrocyte cell number
- more than 3 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 93.2%

schistocytosis

Genotype: Spta1^sph-ha/Spta1⁺
involves: DBA/1J

hematopoietic system phenotype

increased erythrocyte clearance
- 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

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

Additional - Spta1^sph-ha related

Technical Support

Contact Technical Support

Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the WB-hemolytic anemia mouse strain in a publication, please cite the originating article(s) and include JAX stock #000451 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	Genotype	Price
	Heterozygous or wildtype for Spna1<spa-ha>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Payment Terms and Conditions

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.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As: WB-hemolytic anemia

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Spta1sph-ha

Allele Symbol: Spta1sph-ha

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 Genotype

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

Genotype: Spta1sph-ha related

Mammalian Phenotype Terms by Genotype

Genotype: Spta1sph-ha/Spta1sph-hainvolves: DBA/1J

cardiovascular system phenotype

immune system phenotype

integument phenotype

liver/biliary system phenotype

hematopoietic system phenotype

mortality/aging

pigmentation phenotype

reproductive system phenotype

skeleton phenotype

Genotype: Spta1sph-ha/Spta1sph-haeither:(B6.D1-Spta1 x WB.D1-Spta1)F1 or (WB.D1-Spta1 x B6.D1-Spta1)F1

cardiovascular system phenotype

homeostasis/metabolism phenotype

cellular phenotype

immune system phenotype

hematopoietic system phenotype

liver/biliary system phenotype

mortality/aging

respiratory system phenotype

Genotype: Spta1sph-ha/Spta1+either:(B6.D1-Spta1 x WB.D1-Spta1)F1 or (WB.D1-Spta1 x B6.D1-Spta1)F1

hematopoietic system phenotype

homeostasis/metabolism phenotype

Genotype: Spta1sph-ha/Spta1sph-ha(WB.D1-Spta1/Brk x B6.D1-Spta1/Brk)F1

cardiovascular system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

mortality/aging

reproductive system phenotype

hematopoietic system phenotype

Genotype: Spta1sph-ha/Spta1+involves: DBA/1J

hematopoietic system phenotype

References

Additional - Spta1sph-ha 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-ha

Allele Symbol: Spta1^sph-ha

Genotype: Spta1^sph-ha related

Genotype: Spta1^sph-ha/Spta1^sph-ha
involves: DBA/1J

Genotype: Spta1^sph-ha/Spta1^sph-ha
either:(B6.D1-Spta1 x WB.D1-Spta1)F1 or (WB.D1-Spta1 x B6.D1-Spta1)F1

Genotype: Spta1^sph-ha/Spta1⁺
either:(B6.D1-Spta1 x WB.D1-Spta1)F1 or (WB.D1-Spta1 x B6.D1-Spta1)F1

Genotype: Spta1^sph-ha/Spta1^sph-ha
(WB.D1-Spta1/Brk x B6.D1-Spta1/Brk)F1

Genotype: Spta1^sph-ha/Spta1⁺
involves: DBA/1J

Additional - Spta1^sph-ha related