Overview

Also Known As:Hertwig's anemia

These mice carry the spontaneous Hertwig’s anemia mutation (an, now identified to be an allele of the Cdk5rap2 gene) and characterized by a mild macrocytic anemia.

Genetic overview

Genetic Background	Generation

Tyrp1^B-lt

Allele Type	Gene Symbol	Gene Name
Spontaneous	Tyrp1	tyrosinase-related protein 1

Allele Type	Gene Symbol	Gene Name
Radiation induced (Modified isoform(s))	Cdk5rap2	CDK5 regulatory subunit associated protein 2

Research Applications

Hematological Research
Reproductive Biology Research
Research Tools
Cancer Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Homozygous mutants are anemic at birth, are small, and usually die within a few days. The anemia can be seen as early 12 days of gestation and persists throughout life. The white cell count is also much reduced. Adult an/an mice of both sexes have fewer definitive germ cells than do normal littermates and seldom produce offspring. Testicular tubules of newborn an/an males contain primordial germ cells, but almost no spermatogenesis is seen in adult testes. Older an/an mice (beyond 6 to 8 months) frequently develop eye opacities, lose their hair completely, and become emaciated and kyphotic

Development

The mutation Hertwig’s anemia (an) was first described in 1941 as an inherited macrocytic anemia that was identified in the offspring of a heavily irradiated male mouse of undefined genetic background. The mutation has since been identified as an allele of the Cdk5rap2 gene and has been highly backcrossed to the C57BL/6J and the WB/Re inbred strains. A semi-dominant light brown pigment marker, tyrosinase-related protein 1; light (Tryp^B-lt), closely linked to Cdk5rap2^an and fixed on both the WB and B6 an stocks during their development, provides a visible phenotypic marker of +/+, an/+, and an/an mice. The exact date and source for importation of this mutation to The Jackson Laboratory is not known, but in 1968 Dr. Elizabeth Russell was maintaining two strains carrying this mutation. The first was a sibling inbred line referred to as BAN/Re because it was maintained with the b allele of Tyrp1 in coupling with the Cdk5rap2^an mutation and in 1968 this line was at inbreeding generation F22. The second was a congenic line bearing the Cdk5rap2^an mutation in coupling with the semidominant Tyrp1^B-lt allele on the C57BL/6J host background and this congenic was at generation N13 in 1968 and N50 in 1978. This strain was passed from Dr. Russell to Dr. Jane Barker and reached generation N73 in 1986. Sperm was cryopreserved in 2007 from Cdk5rap2^an Tyrp1^B-lt/+ + heterozygous males at generation N96.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Barker JE; Bernstein SE. 1983. Hertwig's anemia: characterization of the stem cell defect. Blood 61(4):765-9PubMed: 6831040 MGI: J:7003
Barker JE; Deveau SA; Compton ST; Fancher K; Eppig JT. 2005. High incidence, early onset of histiocytic sarcomas in mice with Hertwig's anemia. Exp Hematol 33(10):1118-29PubMed: 16219534 MGI: J:102334
Eppig JT; Barker JE. 1984. Chromosome abnormalities in mice with Hertwig's anemia. Blood 64(3):727-32PubMed: 6466874 MGI: J:7537
Hertwig P. 1942. Neue Mutationen und Koppelungsgruppen bei der Hausmaus Z Indukt Abstamm Vererbungsl 80:220-246MGI: J:208
Russell ES; McFarland EC; Peters H. 1985. Gametic and pleiotropic defects in mouse fetuses with Hertwig's macrocytic anemia. Dev Biol 110(2):331-7PubMed: 4018402 MGI: J:7931
Taney FH; Vasilenko P; Steinetz BG; Weiss G; Cole D; Goldsmith LT. 1991. The role of estrogen and relaxin in the reproductive abnormalities of mice with Hertwig's anemia. Biol Reprod 45(5):719-26PubMed: 1756209 MGI: J:753

View All References

Genetics

Tyrp1^B-lt

Allele Symbol: Tyrp1^B-lt

Allele Name	light
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	Tyrp1, tyrosinase-related protein 1
Gene Synonym(s)
Strain of Origin	C58
Chromosome	4
Molecular Note	A C-to-T transition at coding nucleotide 112 is predicted to result in an arginine to cysteine substitition at codon 38 (p.R38C).

Cdk5rap2^an

Allele Symbol: Cdk5rap2^an

Allele Name	Hertwig's anemia
Allele Type	Radiation induced (Modified isoform(s))
Allele Synonym(s)
Gene Symbol and Name	Cdk5rap2, CDK5 regulatory subunit associated protein 2
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	4
Molecular Note	Exon 4 is inverted which results in an in-frame 111 bp deletion with the loss of exon 4 from the mRNA. Northern analysis demonstrated that exon 4 was uniformly omitted from the mutant mRNA.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

microcephaly

Research Areas By Phenotype

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

Genotype: Cdk5rap2^an related

Hematological Research
- Anemia, Iron Homeostasis Defects
- Hematopoietic Defects
Reproductive Biology Research
Research Tools
- Genetics Research
Cancer Research
- Increased Tumor Incidence

Mammalian Phenotype Terms by Genotype

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

Genotype: Cdk5rap2^an/Cdk5rap2^an
Not Specified

cellular phenotype

decreased germ cell number
- reduced number of germ cells starting at E12-E13

decreased oocyte number

immune system phenotype

decreased leukocyte cell number

integument phenotype

premature hair loss
- older survivors (6-8 months) lose their hair completely

mortality/aging

postnatal lethality
- animals die a few days after birth
- most die within a few days or weeks of birth, however a few reach adulthood

neoplasm

increased ovary adenoma incidence
- eventually ovaries become tubular adenomas

reproductive system phenotype

abnormal spermatogenesis
- almost no spermatogenesis is seen in adult testes

decreased germ cell number
- reduced number of germ cells starting at E12-E13

decreased oocyte number

increased ovary adenoma incidence
- eventually ovaries become tubular adenomas

reduced fertility
- survivors are almost completely sterile

skeleton phenotype

kyphosis
- older survivors (6-8 months) become kyphotic

vision/eye phenotype

eye opacity
- older survivors (beyond 6-8 months) frequently develop eye opacities

endocrine/exocrine gland phenotype

increased ovary adenoma incidence
- eventually ovaries become tubular adenomas

growth/size/body region phenotype

decreased body size

hematopoietic system phenotype

abnormal erythrocyte morphology
- mean potential life span of erythrocytes is reduced

abnormal erythropoiesis
- complete regression of hepatic hemopoiesis occurs at about 4 days after birth compared to 10 days in controls
- erythropoiesis is decreased in the liver

anemia
- anemic at birth

anisocytosis

decreased leukocyte cell number

macrocytic anemia

macrocytosis
- seen at birth

reticulocytopenia

Genotype: Cdk5rap2^an/Cdk5rap2^an
involves: C57BL/6 * WB

nervous system phenotype

abnormal cerebral cortex morphology
- cortical hypoplasia visualized by shortening of the forebrain

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

Genotype: Cdk5rap2^an/Cdk5rap2^an
B6.Cg-Cdk5rap2

cellular phenotype

abnormal mitosis

abnormal mitotic spindle morphology
- defective mitotic spindle orientation

abnormal neuron proliferation
- cortical neurons divide less

increased neuron apoptosis
- premature cell cycle exit and increased cell death

growth/size/body region phenotype

decreased body size
- reduced body size at E12.5
- runted

microcephaly
- Background Sensitivity - homozygotes show modest microcephaly on a WBB6F1 background, but more severe on a C57BL/6J congenic background

mortality/aging

premature death
- die within one week of age

nervous system phenotype

abnormal cerebral cortex morphology
- disproportionately reduced cortex

abnormal embryonic/fetal subventricular zone morphology
- reduced ganglionic eminence

abnormal forebrain development
- profound reduction of basal progenitors at later stages in neurogenesis

abnormal neuron proliferation
- cortical neurons divide less

decreased brain size
- brain-to-body weight ratio at P0 is decreased
- reduced brain size at E12.5,

enlarged brain ventricles
- enlarged ventricle

increased neuron apoptosis
- premature cell cycle exit and increased cell death

loss of cortex neurons
- have fewer total neurons and the last-born superficial neurons are particularly reduced

small hippocampus
- at P0 the hippocampus is smaller than wild-type

small olfactory bulb

thin cerebral cortex

References

Barker JE; Bernstein SE. 1983. Hertwig's anemia: characterization of the stem cell defect. Blood 61(4):765-9PubMed: 6831040 MGI: J:7003
Barker JE; Deveau SA; Compton ST; Fancher K; Eppig JT. 2005. High incidence, early onset of histiocytic sarcomas in mice with Hertwig's anemia. Exp Hematol 33(10):1118-29PubMed: 16219534 MGI: J:102334
Eppig JT; Barker JE. 1984. Chromosome abnormalities in mice with Hertwig's anemia. Blood 64(3):727-32PubMed: 6466874 MGI: J:7537
Hertwig P. 1942. Neue Mutationen und Koppelungsgruppen bei der Hausmaus Z Indukt Abstamm Vererbungsl 80:220-246MGI: J:208
Russell ES; McFarland EC; Peters H. 1985. Gametic and pleiotropic defects in mouse fetuses with Hertwig's macrocytic anemia. Dev Biol 110(2):331-7PubMed: 4018402 MGI: J:7931
Taney FH; Vasilenko P; Steinetz BG; Weiss G; Cole D; Goldsmith LT. 1991. The role of estrogen and relaxin in the reproductive abnormalities of mice with Hertwig's anemia. Biol Reprod 45(5):719-26PubMed: 1756209 MGI: J:753

Additional - Cdk5rap2^an related

Additional - Tyrp1^B-lt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Cdk5rap2
- Sanger sequencing:Tyrp1
- Genotyping resources and troubleshooting
Breeding Considerations

The mutation Hertwig’s anemia is separated from the light brown coat color marker by approximately 2 cM. So long as there is no recombination between these loci the mice homozygous for Hertwig’s anemia will be homozygous for the light mutation and can be identified by their light brown coat color, with brown at the tips of the hair and the rest of the shaft almost white. Male homozygotes are sterile, and on the C57BL/6J background few, if any, homozygotes survive. Heterozygotes have increased brown pigment and can be distinguished from homozygotes as early as 2 weeks of age. Black mice are predicted to be wild-type, lacking even one copy of the Hertwig’s anemia mutation, again contingent upon no recombination between these loci.
- Additional Breeding and Husbandry Support
Citation
When using the Hertwig's anemia mouse strain in a publication, please cite the originating article(s) and include JAX stock #002306 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 an

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Cdk5rap2<an> Tyrp1<B-lt>/+ +/BrkJ	$2595.00
Frozen Mouse Embryo	B6.Cg-Cdk5rap2<an> Tyrp1<B-lt>/+ +/BrkJ	$2595.00
Frozen Mouse Embryo	B6.Cg-Cdk5rap2<an> Tyrp1<B-lt>/+ +/BrkJ	$3373.50
Frozen Mouse Embryo	B6.Cg-Cdk5rap2<an> Tyrp1<B-lt>/+ +/BrkJ	$3373.50

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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:Hertwig's anemia

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Tyrp1B-lt

Allele Symbol: Tyrp1B-lt

Cdk5rap2an

Allele Symbol: Cdk5rap2an

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Cdk5rap2an related

Mammalian Phenotype Terms by Genotype

Genotype: Cdk5rap2an/Cdk5rap2anNot Specified

cellular phenotype

immune system phenotype

integument phenotype

mortality/aging

neoplasm

reproductive system phenotype

skeleton phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Cdk5rap2an/Cdk5rap2aninvolves: C57BL/6 * WB

nervous system phenotype

Genotype: Cdk5rap2an/Cdk5rap2anB6.Cg-Cdk5rap2

cellular phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

References

Additional - Cdk5rap2an related

Additional - Tyrp1B-lt related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

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

Tyrp1^B-lt

Allele Symbol: Tyrp1^B-lt

Cdk5rap2^an

Allele Symbol: Cdk5rap2^an

Genotype: Cdk5rap2^an related

Genotype: Cdk5rap2^an/Cdk5rap2^an
Not Specified

Genotype: Cdk5rap2^an/Cdk5rap2^an
involves: C57BL/6 * WB

Genotype: Cdk5rap2^an/Cdk5rap2^an
B6.Cg-Cdk5rap2

Additional - Cdk5rap2^an related

Additional - Tyrp1^B-lt related