Overview

This stock carries two spontaneous mutations, Mitf^Mi-wh (white) and Itpr1^opt (opisthotonus), that affect eye and coat pigmentation, and body movement and balance respectively.

Genetic overview

Genetic Background	Generation

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Itpr1^opt

Allele Type	Gene Symbol	Gene Name
Spontaneous	Itpr1	inositol 1,4,5-trisphosphate receptor 1

Allele Type	Gene Symbol	Gene Name
Spontaneous	Mitf	melanogenesis associated transcription factor

Research Applications

Neurobiology Research
Dermatology Research
Endocrine Deficiency Research
Immunology, Inflammation and Autoimmunity Research
Sensorineural Research
Mouse/Human Gene Homologs

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mutations at the Mitf locus affect eye size, pigmentation, and the capacity for secondary bone resorption. Mice homozygous for the white allele (Mitf^Mi-wh) display an overall absence of pigment cells with the exception of the retina which expresses a few giving the eye a small amount of pigment. Homozygotes show slight microphthalmia but a normal skeleton. Heterozygotes (Mitf^Mi-wh/+) have a diluted coat color, light ears, a white belly spot, and in rare cases a dorsal spot. In addition, they display abnormalities of both the cochlear and vestibular portions of the inner ear. Mice homozygous for the opisthotonus spontaneous mutation (Itpr1^opt) display a characteristic upward arching of head and tail. Homozygous mutant mice can be recognized at about 10 days of age by their loss of balance when standing or moving. Typical behavior of 15 to 20 day old homozygotes consists of falling over and struggling to get up. Agitation and severe opisthotonus ensue with death occuring by weaning age or before.

Control Suggestions

Untyped from the colony

Additional Information

Considerations for Choosing Controls

Genetics

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)	nonagouti; a
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)	agouti signal protein; As; ASP; As; agouti; agouti suppressor; AGTI; SHEP9; AGSW; AGTIL
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
General Note	Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039
Molecular Note	Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.

Itpr1^opt

Allele Symbol: Itpr1^opt

Allele Name	opisthotonus
Allele Type	Spontaneous
Allele Synonym(s)	opisthotonus; Itpr1^opt
Gene Symbol and Name	Itpr1, inositol 1,4,5-trisphosphate receptor 1
Gene Synonym(s)	DNA segment, Chr 6, Pasteur Institute 2; Pcp-1; Pcp1; Ip3r; inositol 1,4,5-triphosphate binding protein; ACV; opt; InsP3R; InsP3R type I; INSP3R1; IP3R; I145TR; Itpr-1; PPP1R94; Itpr-1; opt; Pcp-1; Pcp1; IP3R1; P400; SCA16; SCA29; SCA15; CLA4; Purkinje cell protein 1; opisthotonus; D6Pas2; wobbly locomotion; wblo; wblo; InsP3R1; Ip3r
Strain of Origin	C57BLKS-Lepr^db-2J
Chromosome	6
Molecular Note	The molecular defect underlying the phenotype in the opisthotonus mouse involves a genomic deletion that alters the Itpr1 protein. The genomic deletion removes the first two exons from the mRNA, but does not disrupt the translational reading frame. The protein is reduced in expression and is predicted to have lost several modulatory sites.

Mitf^Mi-wh

Allele Symbol: Mitf^Mi-wh

Allele Name	white
Allele Type	Spontaneous
Allele Synonym(s)	white; Mitf^Mi-wh
Gene Symbol and Name	Mitf, melanogenesis associated transcription factor
Gene Synonym(s)	bHLHe32; BCC2; black eyed white; bw; Gsfbcc2; CMM8; Gsfbcc2; WS2; WS2A; MI; gsf bright coat colour 2; microphthalmia; mi; vit; wh; vitiligo; mi; COMMAD
Strain of Origin	(C57BL x DBA)F1
Chromosome	6
General Note	Combination heterozygotes of Mitf^Mi-wh/Mitf^Mi, Mitf^Mi-wh/Mitf^Mi-b, and Mitf^Mi-wh/Mitf^Mi-ws show some interallelic complementation in that the heterozygote of the two alleles is more nearly normal than either homozygote (J:12967, J:19656). Mitf^Mi-b/Mitf^Mi-wh agouti mice are light cream with white spots and ruby eyes (J:15061).
Molecular Note	T to A transversion at bp 764, which leads to an isoleucine to asparagine substitution at the corresponding amino acid (212) in the encoded protein. This mutation is in the basic region of the protein.

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).

Research Areas By Genotype

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

Genotype: Itpr1^opt related

Neurobiology Research
- Epilepsy
- Metabolic Defects
- Receptor Defects

Genotype: Mitf^Mi-wh related

Dermatology Research
- Color and White Spotting Defects
Endocrine Deficiency Research
- Bone/Bone Marrow Defects
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects
Neurobiology Research
- Hearing Defects
Sensorineural Research
- Eye Defects
- Hearing Defects
Mouse/Human Gene Homologs
- Waardenburg syndrome, type IIA

Mammalian Phenotype Terms by Genotype

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

Genotype: Itpr1^opt/Itpr1^opt
involves: C57BLKS

behavior/neurological phenotype

abnormal locomotor behavior
- abnormal locomotor ability

abnormal locomotor coordination
- abnormal walking

impaired balance
- at 10 days of age, mice exhibit a loss of balance when standing or moving
- at 15-20 days of age, mice constantly fall over on their sides

impaired coordination

impaired righting response
- at 15-20 days of age, mice struggle to right themselves

opisthotonus
- severe after 15-20 days of age

seizures
- range from subtle tremors to marked convulsions; progressive severity with age
- visible seizures appear by P14; range from body tremors to full tonic clonic convulsions; progressive with age

weakness
- weak and sickly appearance by 7 days of age

cellular phenotype

abnormal cell physiology
- quisqualate (QA) treatment of Purkinje neurons elicited a similar calcium release as controls; repeated QA application showed a less attenuated response in mutant cells than in controls

growth/size/body region phenotype

decreased body size
- reported as smaller than littermates

mammalian phenotype

nervous system phenotype
- Normal - gross anatomy of the cerebellum appears normal
- Normal - normal cerebellum morphology; normal numbers and morphology of Purkinje cells

mortality/aging

lethality at weaning, complete penetrance
- mice die at 3-4 weeks of age
- mice die by weaning age or earlier

muscle phenotype

opisthotonus
- severe after 15-20 days of age

nervous system phenotype

seizures
- range from subtle tremors to marked convulsions; progressive severity with age
- visible seizures appear by P14; range from body tremors to full tonic clonic convulsions; progressive with age

Genotype: Mitf^Mi-wh/Mitf^Mi-wh
involves: C57BL * DBA

growth/size/body region phenotype

decreased body size
- reduced body size compared to f Tyr^c homozygotes

reproductive system phenotype

decreased litter size
- litter size is reduced in homozygous female to homozygous male crosses

reduced fertility

vision/eye phenotype

decreased eye pigmentation
- little or no pigment in the iris

microphthalmia
- eye size appears reduced compared to f Tyr^c homozygotes
- the eyes are only mildly reduced in size

ocular albinism
- eyes are pink and pigmentless

hearing/vestibular/ear phenotype

abnormal cochlea morphology
- no section of the cochlear duct was ever found to be normal

abnormal cochlear hair cell morphology

abnormal stria vascularis morphology
- abnormal in its entirety

abnormal vestibular saccule morphology
- the majority of ears show dedifferentiation and cellular migrations in the cochlear duct and the saccule

integument phenotype

absent coat pigmentation
- coat color is indistinguishable from that of Tyr^c homozygotes
- the coat is entirely lacking pigment

nervous system phenotype

abnormal cochlear hair cell morphology

pigmentation phenotype

absent coat pigmentation
- coat color is indistinguishable from that of Tyr^c homozygotes
- the coat is entirely lacking pigment

decreased eye pigmentation
- little or no pigment in the iris

ocular albinism
- eyes are pink and pigmentless

Genotype: Mitf^Mi-wh/Mitf⁺
involves: C57BL * DBA

integument phenotype

abnormal foot pigmentation
- reduced foot pigmentation

decreased tail pigmentation
- reduced tail pigmentation

diluted coat color
- coat color darkens slightly with age
- coat color is gray and somewhat lighter than that of Myo5a^d homozygotes

white spotting
- small spots may occur on the back, but spotting is not found on the head

vision/eye phenotype

abnormal iris pigmentation
- moderate dilution of the iris pigmentation

decreased eye pigmentation
- eyes are a very dark ruby color

limbs/digits/tail phenotype

decreased tail pigmentation
- reduced tail pigmentation

pigmentation phenotype

abnormal foot pigmentation
- reduced foot pigmentation

abnormal iris pigmentation
- moderate dilution of the iris pigmentation

decreased eye pigmentation
- eyes are a very dark ruby color

decreased tail pigmentation
- reduced tail pigmentation

diluted coat color
- coat color darkens slightly with age
- coat color is gray and somewhat lighter than that of Myo5a^d homozygotes

white spotting
- small spots may occur on the back, but spotting is not found on the head

Genotype: Mitf^Mi-wh/Mitf^Mi-wh
B6.Cg-Mitf

homeostasis/metabolism phenotype

decreased bleeding time
- bleed time of only 1 minute after tail nick is significantly less than the 3.8 minutes in C57BL/6J controls

vision/eye phenotype

abnormal optic choroid morphology
- at birth the choroid fissure is irregularly closed in the anterior eye and open from the posterior part of the lens to the rear of the optic cup
- in newborns the retinal eversion remains obvious in the unclosed portions of the choroid fissure

abnormal optic cup morphology
- irregularly formed surrounding less than half of the spherical lens
- slightly reduced in size from E13 onwards

abnormal optic fissure closure
- at E12 the choroid fissure is mostly closed but the joining of the retinal nervous layer is not smooth and a large retinal eversion is present at the rear of the optic cup where the fissure fails to close
- in newborns the retinal eversion remains obvious in the unclosed portions of the choroid fissure

abnormal optic stalk morphology
- shorter and somewhat greater in diameter at E11.5 and E12
- slight increase in diameter at E11

abnormal posterior eye segment morphology
- the lens fills the space normally occupied by the vitreous body

abnormal retinal neuronal layer morphology
- at birth, the layers are less clearly defined

abnormal retinal pigment epithelium morphology
- after E12 in some area the cells are columnar rather than cuboidal
- at all stages the number of mitoses is increased compared to control pigment layers
- at E11.5 and E12, the pigment layer is irregullar, mainly in the dorsal region
- pigment granules are absent at E11

abnormal retinal pigmentation
- after E12, a few pigment granules may be found in the front edge of the pigment layer
- at birth a few pigment granules are present near the iris
- pigment granules are absent from the pigment layer at E11

microphthalmia
- slightly smaller at birth

mammalian phenotype

skeleton phenotype
- unlike Mitf^Mi homozygotes no skeletal abnormalities are seen

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- after E12 in some area the cells are columnar rather than cuboidal
- at all stages the number of mitoses is increased compared to control pigment layers
- at E11.5 and E12, the pigment layer is irregullar, mainly in the dorsal region
- pigment granules are absent at E11

abnormal retinal pigmentation
- after E12, a few pigment granules may be found in the front edge of the pigment layer
- at birth a few pigment granules are present near the iris
- pigment granules are absent from the pigment layer at E11

Genotype: Mitf^Mi-wh/Mitf^Mi-wh
involves: C57BL * C57BL/6J * DBA

integument phenotype

absent coat pigmentation
- white coat

mammalian phenotype

skeleton phenotype
- Normal - normal bone development and mice do not develop osteopetrosis

pigmentation phenotype

absent coat pigmentation
- white coat

decreased eye pigmentation
- eyes are slightly pigmented

vision/eye phenotype

decreased eye pigmentation
- eyes are slightly pigmented

microphthalmia

References

Additional References

Hodgkinson CA; Moore KJ; Nakayama A; Steingrimsson E; Copeland NG; Jenkins NA; Arnheiter H. 1993. Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell 74(2):395-404PubMed: 8343963 MGI: J:13562
Tachibana M; Perez-Jurado LA; Nakayama A; Hodgkinson CA; Li X; Schneider M; Miki T; Fex J; Francke U; Arnheiter H. 1994. Cloning of MITF, the human homolog of the mouse microphthalmia gene and assignment to chromosome 3p14.1-p12.3. Hum Mol Genet 3(4):553-7PubMed: 8069297 MGI: J:17853
Steingrimsson E; Moore KJ; Lamoreux ML; Ferre-D'Amare AR; Burley SK; Zimring DC; Skow LC; Hodgkinson CA; Arnheiter H; Copeland NG; Jenkins NA. 1994. Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences [see comments] Nat Genet 8(3):256-63PubMed: 7874168 MGI: J:21366
Motohashi H; Hozawa K; Oshima T; Takeuchi T; Takasaka T. 1994. Dysgenesis of melanocytes and cochlear dysfunction in mutant microphthalmia (mi) mice. Hear Res 80(1):10-20PubMed: 7852195 MGI: J:21682
Street VA; Bosma MM; Demas VP; Regan MR; Lin DD; Robinson LC ; Agnew WS ; Tempel BL. 1997. The type 1 inositol 1,4,5-trisphosphate receptor gene is altered in the opisthotonos mouse. J Neurosci 17(2):635-45PubMed: 8987786 MGI: J:37547
Deol MS. 1967. The neural crest and the acoustic ganglion. J Embryol Exp Morphol 17(3):533-41PubMed: 6049665 MGI: J:5048
Raisz LG; Simmons HA; Gworek SC; Eilon G. 1977. Studies on congenital osteopetrosis in microphthalmic mice using organ cultures: impairment of bone resorption in response to physiologic stimulators. J Exp Med 145(4):857-65PubMed: 870607 MGI: J:5804

Additional - a related

Additional - Itpr1^opt related

Additional - Mitf^Mi-wh related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR:Itpr1^opt
- Genotyping resources and troubleshooting
Breeding Considerations

Mitf and Itpr^opt are linked on chromosome 6 and are maintained in repulsion in this strain. Iptr^opt/opt die by wean age. Mitf^Mi-wh/Mi-wh are white and Mitf^Mi-wh/+ are black with a white head dot and belly spot.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK a/a Mitf^Mi-wh +/+ Itpr1^opt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000302 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
	Homozygous for a, Heterozygous for Mi<Wh>, Heterozygous for opt

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.

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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.

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

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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.

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Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

a

Allele Symbol: a

Itpr1opt

Allele Symbol: Itpr1opt

MitfMi-wh

Allele Symbol: MitfMi-wh

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).

Research Areas By Genotype

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

Genotype: Itpr1opt related

Genotype: MitfMi-wh related

Mammalian Phenotype Terms by Genotype

Genotype: Itpr1opt/Itpr1optinvolves: C57BLKS

behavior/neurological phenotype

cellular phenotype

growth/size/body region phenotype

mammalian phenotype

mortality/aging

muscle phenotype

nervous system phenotype

Genotype: MitfMi-wh/MitfMi-whinvolves: C57BL * DBA

growth/size/body region phenotype

reproductive system phenotype

vision/eye phenotype

hearing/vestibular/ear phenotype

integument phenotype

nervous system phenotype

pigmentation phenotype

Genotype: MitfMi-wh/Mitf+involves: C57BL * DBA

integument phenotype

vision/eye phenotype

limbs/digits/tail phenotype

pigmentation phenotype

Genotype: MitfMi-wh/MitfMi-whB6.Cg-Mitf

homeostasis/metabolism phenotype

vision/eye phenotype

mammalian phenotype

pigmentation phenotype

Genotype: MitfMi-wh/MitfMi-whinvolves: C57BL * C57BL/6J * DBA

integument phenotype

mammalian phenotype

pigmentation phenotype

vision/eye phenotype

References

Additional References

Additional - a related

Additional - Itpr1opt related

Additional - MitfMi-wh 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

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

Itpr1^opt

Allele Symbol: Itpr1^opt

Mitf^Mi-wh

Allele Symbol: Mitf^Mi-wh

Genotype: Itpr1^opt related

Genotype: Mitf^Mi-wh related

Genotype: Itpr1^opt/Itpr1^opt
involves: C57BLKS

Genotype: Mitf^Mi-wh/Mitf^Mi-wh
involves: C57BL * DBA

Genotype: Mitf^Mi-wh/Mitf⁺
involves: C57BL * DBA

Genotype: Mitf^Mi-wh/Mitf^Mi-wh
B6.Cg-Mitf

Genotype: Mitf^Mi-wh/Mitf^Mi-wh
involves: C57BL * C57BL/6J * DBA

Additional - Itpr1^opt related

Additional - Mitf^Mi-wh related