Overview

Also Known As:microphthalmia

These Mitf^Mi mutant mice are characterized by small eyes, and lack of pigment in the eyes, inner ear, and skin, and early deafness. White spotting on the belly, head, and tail are common.

Genetic overview

Genetic Background	Generation

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

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

Research Applications

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

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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 heterozygous for the Mitf^Mi mutation have less iris pigment than wildtype and often have white spotting on the belly, head, and tail. Homozygous mutant mice have small eyes and are devoid of pigment in the eyes, inner ear, and skin. Homozygotes are deaf at an early age. There is a decrease of mast cells in the spleen and gut. Most homozygotes die around weaning but some may live for several months. There is a deficiency of secondary bone resorption (osteopetrosis) and the incisors fail to erupt. Immunological defects include decreased macrophage chemotactic responses, impaired proliferative responses to B cell and T cell mitogens, diminished responses in vitro to T-dependent and T-independent antigens and reduced NK cell activity.

Development

The semi-dominant mutation microphthalmia (Mitf^Mi) was found among descendants of an irradiated male by Hertwig before 1942. It was sent to Dr. E.S. Russell at The Jackson Laboratory from Dr. Hans Gruneberg in 1961. It was maintained with the dominant allele Mitf^Mi-wh and crossed to C57BL/6J as Mitf^Mi-wh/Mitf^Mi each N generation until 1986 at N100. It was then backcrossed to C57BL/6J without Mitf^Mi-wh to N105. A cross was then made of a host female bearing a C57BL/6J-Mitf^Mi homozygous ovary to a C3HeB/FeJ-a/a male. The strain was then maintained by mating to the hybrid B6C3Fe-a/a each cross generation and mating the offspring each intercross generation.

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)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
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.

Mitf^Mi

Allele Symbol: Mitf^Mi

Allele Name	microphthalmia
Allele Type	Other
Allele Synonym(s)	m; mi
Gene Symbol and Name	Mitf, melanogenesis associated transcription factor
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	6
General Note	This mutation produces an osteopetrosis that resembles human osteopetrosis more than that produced by Ctsf^op. Mitf^Mi mutant mice have normal levels of M-CSF and its receptor. Osteoplasts are produced, but are unable to function normally in bone resorption (J:22788). Combination heterozygotes of Mitf^Mi-wh/Mitf^Mi show some interallelic complementation in that the heterozygote of the two alleles is more nearly normal than either homozygote (J:12967). Mitf^Mi-Or/Mitf^Mi mice resemble homozygous Mitf^Mi-Or (J:15060).
Molecular Note	This mutation was identified during an irradiation experiment, but it is not known whether it was induced in the treated male or spontaneously arose in an untreated mate. RT-PCR analysis identified a 3 nucleotide deletion in the transcript that results in a loss of one of four conserved arginine residues in the basic domain of the encoded protein. This mutation is predicted to affect the ability of the protein to bind DNA.

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 Phenotype

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

Genotype: Mitf^Mi related

Sensorineural Research
- Eye Defects
- Hearing Defects
Developmental Biology Research
- Skeletal Defects
  - osteopetrosis
- Neural Crest Defects
Mouse/Human Gene Homologs
- Waardenburg syndrome, type IIA
Hematological Research
- Mast Cell Deficiency
  - osteopetrosis
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

Developmental Biology Research
- Skeletal Defects
  - osteopetrosis
Internal/Organ Research
- Skeleton
  - Bone

Mammalian Phenotype Terms by Genotype

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

Genotype: Mitf^Mi/Mitf^Mi
Not Specified

craniofacial phenotype

failure of tooth eruption
- incisors fail to erupt

immune system phenotype

abnormal osteoclast morphology
- cells are smaller, rounder, and contain fewer nuclei than in heterozygous controls
- cells contain greater amounts of cytoplasmic basophilia and cytoplasmic RNA compared to heterozygous controls
- the ratio of regular to irregular nuclei is significantly greater in homozygotes compared to heterozygous controls

decreased mast cell number
- deficiency in gut and liver

increased osteoclast cell number
- increase in the number of osteoclasts on the parietal bones of most homozygotes at P0, P3, P7.5 and P10 compared to heterozygous controls

integument phenotype

absent coat pigmentation
- homozygotes are white

growth/size/body region phenotype

failure of tooth eruption
- incisors fail to erupt

mortality/aging

decreased survivor rate
- viability is very low

postnatal lethality
- most die at weaning but infrequently some live several months

nervous system phenotype

abnormal cochlear hair cell morphology

absent optic nerve
- at P0, the optic canal is open and nerve fibers pass toward the brain along the optic stalk; however, no defined optic nerve is present

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- at all stages the mitotic values in the pigment layer is increased compared to controls
- at E10.5 the pigment layer is thicker than in control littermates and this is more prominent dorsally where the layer is irregular
- at E11.5 layer thickness is increased and dorsal regions are particularly thickened and wavy
- at E11.5, this layer is a thickened monolayer ventrally and an irregular multilayered structure dorsally
- at P0 folds are present
- at P0, the ventral and ventral lateral portions of the layer are mainly a cuboidal monolayer while the dorsal and dorsal-lateral areas are composed of columnar cells in irregular multiple layers

abnormal retinal pigmentation
- complete absence of pigment granules at E11.5 and at P0

absent coat pigmentation
- homozygotes are white

decreased eye pigmentation

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 scala media 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

skeleton phenotype

abnormal osteoclast morphology
- cells are smaller, rounder, and contain fewer nuclei than in heterozygous controls
- cells contain greater amounts of cytoplasmic basophilia and cytoplasmic RNA compared to heterozygous controls
- the ratio of regular to irregular nuclei is significantly greater in homozygotes compared to heterozygous controls

abnormal skeleton morphology

failure of tooth eruption
- incisors fail to erupt

increased osteoclast cell number
- increase in the number of osteoclasts on the parietal bones of most homozygotes at P0, P3, P7.5 and P10 compared to heterozygous controls

osteopetrosis
- cells show defects in function and hormone response and fusion disability
- probable defect is in progenitor osteoclasts and can be transmitted via transplanted spleen and bone marrow cells

vision/eye phenotype

abnormal ciliary body morphology
- thicker and less folded than in control littermates at P0

abnormal eye development
- at all stages the mitotic values in the pigment layer is increased compared to controls
- at E10.5 - E12 the average number of mitoses in the nervous layer of the retina is increased1.2 to 1.4 times compared to controls; however unlike in controls the number of mitoses does not increase from E14 - E16

abnormal optic choroid morphology
- remains open at E12 and in areas along the edges inversion of the pigment epithelium is seen

abnormal optic cup morphology
- abnormal morphology persists through E11.5
- arching of the cup is reduced and the medial-lateral diameter is increased at E10.5
- at P0 the cup is poorly arched around the lens

abnormal optic stalk morphology
- abnormal morphology persists through E11.5
- increased diameter of the stalk at E10.5
- optic stalk is still present at E14, E16, and P0 when in control littermates it is nearly or completely absent

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

abnormal retinal neuronal layer morphology
- at E10.5 - E12 the average number of mitoses in the nervous layer of the retina is increased1.2 to 1.4 times compared to controls; however unlike in controls the number of mitoses does not increase from E14 - E16
- the nervous layer is irregular in thickness, folded and the strata are less clearly defined

abnormal retinal pigment epithelium morphology
- at all stages the mitotic values in the pigment layer is increased compared to controls
- at E10.5 the pigment layer is thicker than in control littermates and this is more prominent dorsally where the layer is irregular
- at E11.5 layer thickness is increased and dorsal regions are particularly thickened and wavy
- at E11.5, this layer is a thickened monolayer ventrally and an irregular multilayered structure dorsally
- at P0 folds are present
- at P0, the ventral and ventral lateral portions of the layer are mainly a cuboidal monolayer while the dorsal and dorsal-lateral areas are composed of columnar cells in irregular multiple layers

abnormal retinal pigmentation
- complete absence of pigment granules at E11.5 and at P0

absent optic nerve
- at P0, the optic canal is open and nerve fibers pass toward the brain along the optic stalk; however, no defined optic nerve is present

coloboma
- at E16, the optic canal is open to the brain and this coloboma extends along the entire ventral surface of the optic cup and optic stalk
- at P0, the coloboma is wider at its anterior edge with overlapping edges in the posterior region and inversion of the pigmented layer is seen along one or both edges
- in anterior regions the edges of the coloboma do not meet while in ventral regions the edges overlap

decreased eye pigmentation

eyelids fail to open

microphthalmia
- first detectable at E14, becoming more obvious with age
- the eyes are severely reduced in size

hematopoietic system phenotype

abnormal osteoclast morphology
- cells are smaller, rounder, and contain fewer nuclei than in heterozygous controls
- cells contain greater amounts of cytoplasmic basophilia and cytoplasmic RNA compared to heterozygous controls
- the ratio of regular to irregular nuclei is significantly greater in homozygotes compared to heterozygous controls

decreased mast cell number
- deficiency in gut and liver

increased osteoclast cell number
- increase in the number of osteoclasts on the parietal bones of most homozygotes at P0, P3, P7.5 and P10 compared to heterozygous controls

Genotype: Mitf^Mi/Mitf⁺
Not Specified

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

nervous system phenotype

abnormal cochlear hair cell morphology

pigmentation phenotype

abnormal coat/hair pigmentation
- slight dilution of the fur in the young returns to normal in the adult

abnormal iris stromal pigmentation
- less iris pigment than normal

belly spot

decreased eye pigmentation
- iris pigmentation is reduced

head spot

white spotting
- some, but not all, heterozygotes have a small spot on the head between the eyes and ears or spots on the belly or tail
- white regions on tail

vision/eye phenotype

abnormal iris stromal pigmentation
- less iris pigment than normal

decreased eye pigmentation
- iris pigmentation is reduced

integument phenotype

abnormal coat/hair pigmentation
- slight dilution of the fur in the young returns to normal in the adult

belly spot

head spot

white spotting
- some, but not all, heterozygotes have a small spot on the head between the eyes and ears or spots on the belly or tail
- white regions on tail

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

hematopoietic system phenotype

abnormal mast cell physiology
- cultured mast cells exhibit no cytotoxicity towards YAC-1 cells unlike wild-type mast cells
- serotonin concentrations in cultured mast cells are lower than in wild-type cells

homeostasis/metabolism phenotype

decreased serotonin level
- serotonin concentrations in cultured mast cells are lower than in wild-type cells

immune system phenotype

abnormal mast cell physiology
- cultured mast cells exhibit no cytotoxicity towards YAC-1 cells unlike wild-type mast cells
- serotonin concentrations in cultured mast cells are lower than in wild-type cells

nervous system phenotype

decreased serotonin level
- serotonin concentrations in cultured mast cells are lower than in wild-type cells

Genotype: Mitf^Mi/Mitf^Mi
involves: C57BL/6J

craniofacial phenotype

failure of tooth eruption
- incisors fail to erupt

vision/eye phenotype

microphthalmia

growth/size/body region phenotype

decreased body size
- mice are half the normal size

failure of tooth eruption
- incisors fail to erupt

hematopoietic system phenotype

abnormal osteoclast morphology
- small osteoclasts

immune system phenotype

abnormal osteoclast morphology
- small osteoclasts

integument phenotype

absent coat pigmentation
- white coat

mortality/aging

postnatal lethality
- mice do not live past 3 weeks of age

pigmentation phenotype

absent coat pigmentation
- white coat

skeleton phenotype

abnormal osteoclast morphology
- small osteoclasts

failure of tooth eruption
- incisors fail to erupt

osteopetrosis
- severe osteopetrosis, with extensive accumulation of unresorbed endochondral bone and no bone marrow cavity

References

Additional References

Deol MS. 1967. The neural crest and the acoustic ganglion. J Embryol Exp Morphol 17(3):533-41PubMed: 6049665 MGI: J:5048
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
Luchin A; Suchting S; Merson T; Rosol TJ; Hume DA; Cassady AI; Ostrowski MC. 2001. Genetic and physical interactions between Microphthalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation. J Biol Chem 276(39):36703-10PubMed: 11481336 MGI: J:71813
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
Potterf SB; Mollaaghababa R; Hou L; Southard-Smith EM; Hornyak TJ; Arnheiter H; Pavan WJ. 2001. Analysis of sox10 function in neural crest-derived melanocyte development: sox10-dependent transcriptional control of dopachrome tautomerase. Dev Biol 237(2):245-57PubMed: 11543611 MGI: J:71587
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
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
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
Tagaya H; Kunisada T; Yamazaki H; Yamane T; Tokuhisa T; Wagner EF; Sudo T; Shultz LD; Hayashi SI. 2000. Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice. Blood 95(11):3363-70PubMed: 10828017 MGI: J:82593

Additional - a related

Additional - Mitf^Mi related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Mitf
- Genotyping resources and troubleshooting
Appearance
- albino, small eyes
  Related Genotype: a/a Mitf^Mi/Mitf^Mi
  
  black
  Related Genotype: a/a Mitf^Mi/+ or a/a +/+
  
  black with white spotting
  Related Genotype: some a/a Mitf^Mi/+
Citation
When using the microphthalmia mouse strain in a publication, please cite the originating article(s) and include JAX stock #001573 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 Mitf<Mi>

Related Products and Services

Frozen Mouse Embryo	B6C3Fe a/a-Mitf<Mi>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6C3Fe a/a-Mitf<Mi>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6C3Fe a/a-Mitf<Mi>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6C3Fe a/a-Mitf<Mi>/J Frozen Embryo	$3373.50

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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:microphthalmia

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

a

Allele Symbol: a

MitfMi

Allele Symbol: MitfMi

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 Phenotype

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

Genotype: MitfMi related

Mammalian Phenotype Terms by Genotype

Genotype: MitfMi/MitfMiNot Specified

craniofacial phenotype

immune system phenotype

integument phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

pigmentation phenotype

hearing/vestibular/ear phenotype

skeleton phenotype

vision/eye phenotype

hematopoietic system phenotype

Genotype: MitfMi/Mitf+Not Specified

hearing/vestibular/ear phenotype

nervous system phenotype

pigmentation phenotype

vision/eye phenotype

integument phenotype

Genotype: MitfMi/MitfMiB6.Cg-Mitf

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

nervous system phenotype

Genotype: MitfMi/MitfMiinvolves: C57BL/6J

craniofacial phenotype

vision/eye phenotype

growth/size/body region phenotype

hematopoietic system phenotype

immune system phenotype

integument phenotype

mortality/aging

pigmentation phenotype

skeleton phenotype

References

Additional References

Additional - a related

Additional - MitfMi related

Genotyping Protocols

Appearance

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

Mitf^Mi

Allele Symbol: Mitf^Mi

Genotype: Mitf^Mi related

Genotype: Mitf^Mi/Mitf^Mi
Not Specified

Genotype: Mitf^Mi/Mitf⁺
Not Specified

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

Genotype: Mitf^Mi/Mitf^Mi
involves: C57BL/6J

Additional - Mitf^Mi related