Mouse Genome Informatics
hm1
    MitfMi/MitfMi
B6.Cg-MitfMi
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• serotonin concentrations in cultured mast cells are lower than in wild-type cells
• cultured mast cells exhibit no cytotoxicity towards YAC-1 cells unlike wild-type mast cells

homeostasis/metabolism
• serotonin concentrations in cultured mast cells are lower than in wild-type cells

hematopoietic system
• serotonin concentrations in cultured mast cells are lower than in wild-type cells
• cultured mast cells exhibit no cytotoxicity towards YAC-1 cells unlike wild-type mast cells


Mouse Genome Informatics
hm2
    MitfMi/MitfMi
involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice do not live past 3 weeks of age

growth/size
• incisors fail to erupt
• mice are half the normal size

hematopoietic system
• small osteoclasts

immune system
• small osteoclasts

craniofacial
• incisors fail to erupt

pigmentation

skeleton
• small osteoclasts
• severe osteopetrosis, with extensive accumulation of unresorbed endochondral bone and no bone marrow cavity

vision/eye

integument


Mouse Genome Informatics
hm3
    MitfMi/MitfMi
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

MitfMi/MitfMi and control

mortality/aging
• viability is very low
• most die at weaning but infrequently some live several months

pigmentation
• homozygotes are white (J:125080)
• 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, this layer is a thickened monolayer ventrally and an irregular multilayered structure dorsally
• at E11.5 layer thickness is increased and dorsal regions are particularly thickened and wavy
• 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
• at P0 folds are present
• at all stages the mitotic values in the pigment layer is increased compared to controls
• complete absence of pigment granules at E11.5 and at P0

skeleton
• cells are smaller, rounder, and contain fewer nuclei than in heterozygous controls
• the ratio of regular to irregular nuclei is significantly greater in homozygotes compared to heterozygous controls
• cells contain greater amounts of cytoplasmic basophilia and cytoplasmic RNA compared to heterozygous controls
• increase in the number of osteoclasts on the parietal bones of most homozygotes at P0, P3, P7.5 and P10 compared to heterozygous controls
• probable defect is in progenitor osteoclasts and can be transmitted via transplanted spleen and bone marrow cells
• cells show defects in function and hormone response and fusion disability

vision/eye
• thicker and less folded than in control littermates at P0
• 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
• at all stages the mitotic values in the pigment layer is increased compared to controls
• arching of the cup is reduced and the medial-lateral diameter is increased at E10.5
• abnormal morphology persists through E11.5
• at P0 the cup is poorly arched around the lens
• increased diameter of the stalk at E10.5
• abnormal morphology persists through E11.5
• optic stalk is still present at E14, E16, and P0 when in control littermates it is nearly or completely absent
• 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
• in anterior regions the edges of the coloboma do not meet while in ventral regions the edges overlap
• 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
• first detectable at E14, becoming more obvious with age (J:5046)
• the eyes are severely reduced in size (J:125080)
• the lens fills the space normally occupied by the vitreous body
• 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
• 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, this layer is a thickened monolayer ventrally and an irregular multilayered structure dorsally
• at E11.5 layer thickness is increased and dorsal regions are particularly thickened and wavy
• 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
• at P0 folds are present
• at all stages the mitotic values in the pigment layer is increased compared to controls
• complete absence of pigment granules at E11.5 and at P0
• the nervous layer is irregular in thickness, folded and the strata are less clearly defined
• 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
• remains open at E12 and in areas along the edges inversion of the pigment epithelium is seen

immune system
• deficiency in gut and liver
• cells are smaller, rounder, and contain fewer nuclei than in heterozygous controls
• the ratio of regular to irregular nuclei is significantly greater in homozygotes compared to heterozygous controls
• cells contain greater amounts of cytoplasmic basophilia and cytoplasmic RNA compared to heterozygous controls
• increase in the number of osteoclasts on the parietal bones of most homozygotes at P0, P3, P7.5 and P10 compared to heterozygous controls

nervous system
• 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

craniofacial
• incisors fail to erupt

hematopoietic system
• deficiency in gut and liver
• cells are smaller, rounder, and contain fewer nuclei than in heterozygous controls
• the ratio of regular to irregular nuclei is significantly greater in homozygotes compared to heterozygous controls
• cells contain greater amounts of cytoplasmic basophilia and cytoplasmic RNA compared to heterozygous controls
• increase in the number of osteoclasts on the parietal bones of most homozygotes at P0, P3, P7.5 and P10 compared to heterozygous controls

hearing/vestibular/ear
• no section of the cochlear duct was ever found to be normal
• abnormal in its entirety
• the majority of ears show dedifferentiation and cellular migrations in the cochlear duct and the saccule

integument
• homozygotes are white (J:125080)

growth/size
• incisors fail to erupt


Mouse Genome Informatics
ht4
    MitfMi/Mitf+
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• slight dilution of the fur in the young returns to normal in the adult
• white regions on tail (J:30758)
• some, but not all, heterozygotes have a small spot on the head between the eyes and ears or spots on the belly or tail (J:125080)
• less iris pigment than normal
• iris pigmentation is reduced

vision/eye
• less iris pigment than normal
• iris pigmentation is reduced

hearing/vestibular/ear
• no section of the cochlear duct was ever found to be normal
• abnormal in its entirety
• the majority of ears show dedifferentiation and cellular migrations in the cochlear duct and the saccule

nervous system

integument
• slight dilution of the fur in the young returns to normal in the adult
• white regions on tail (J:30758)
• some, but not all, heterozygotes have a small spot on the head between the eyes and ears or spots on the belly or tail (J:125080)


Mouse Genome Informatics
ht5
    MitfMi/Mitfmi-sp
B6.Cg-MitfMi/Mitfmi-sp
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• by backcross generation N5 the coat color is all white with all hair devoid of pigment
• ruby colored eyes

vision/eye
• ruby colored eyes

integument
• by backcross generation N5 the coat color is all white with all hair devoid of pigment


Mouse Genome Informatics
ht6
    MitfMi/Mitftm1Arnh
involves: 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• mice have a white coat color rarely with some dark spots

vision/eye
N
• mice have normal size eyes compared to the small eyes in mice with homozygous null alleles of this gene (J:130168)

integument
• mice have a white coat color rarely with some dark spots


Mouse Genome Informatics
ht7
    Mitftm4Arnh/MitfMi
involves: 129S6/SvEvTac * C57BL/6N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• white with occasional small black spots

integument
• white with occasional small black spots


Mouse Genome Informatics
ht8
    Mitftm5Arnh/MitfMi
involves: 129S6/SvEvTac * C57BL/6N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• white with occasional small black spots

integument
• white with occasional small black spots


Mouse Genome Informatics
ht9
    Mitftm6Arnh/MitfMi
involves: 129S6/SvEvTac * C57BL/6N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• white with occasional small black spots

integument
• white with occasional small black spots


Mouse Genome Informatics
ht10
    Mitftm7Arnh/MitfMi
involves: 129S6/SvEvTac * C57BL/6N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• white with occasional small black spots

integument
• white with occasional small black spots


Mouse Genome Informatics
ht11
    MitfMi/MitfMi-J
involves: C3HeB/Fe * C57BL/6J * C57BL/10J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument

pigmentation

vision/eye


Mouse Genome Informatics
ht12
    MitfMi/Mitfmi-sp
involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• Background Sensitivity: prior to backcross generation N5 on the C57BL/6J background mice are white except for a variable number of faint irregular pigment patches; the faint dorsal pigmentation is lost with further backcrossing (J:12946)
• ruby colored eyes

vision/eye
• ruby colored eyes


Mouse Genome Informatics
cx13
    MitfMi/MitfMi
Tfectm1Est/Tfectm1Est

either: (involves: 129/Sv * 129S1/Sv * C57BL/6J) or (involves: 129S1/Sv * C57BL/6J)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation

skeleton

vision/eye

integument


Mouse Genome Informatics
cx14
    MitfMi/MitfMi
Tfe3tm1Est/Tfe3tm1Est

either: (involves: 129/Sv * 129S1/Sv * C57BL/6J) or (involves: 129S1/Sv * C57BL/6J)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• small osteoclasts (J:89821)

immune system
• small osteoclasts (J:89821)

pigmentation
• white coat (J:89821)

skeleton
• small osteoclasts (J:89821)
(J:89821)

vision/eye
(J:89821)

integument
• white coat (J:89821)


Mouse Genome Informatics
cx15
    MitfMi/Mitf+
Vsx2tm1.1Itl/Vsx2tm1.1Itl

involves: 129S1/Sv * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

The dominant negative MitfMi allele restores retinal development in the Vsx2 mutants

vision/eye
• substantial improvements in eye size, tissue histology and retinal neurogenesis compared to mice homozygous for Vsx2tm1.1Itl alone
• substantial improvements in eye size compared to mice homozygous for Vsx2tm1.1Itl alone


Mouse Genome Informatics
cx16
    MitfMi/Mitf+
Vsx2or-J/Vsx2or-J

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

The dominant negative MitfMi allele restores retinal development in the Vsx2 mutants

vision/eye
• substantial improvements in eye size, tissue histology and retinal neurogenesis compared to mice homozygous for Vsx2or-J alone
• substantial improvements in eye size compared to mice homozygous for Vsx2or-J alone


Mouse Genome Informatics
cx17
    MitfMi/Mitf+
Vsx2tm1.1Eml/Vsx2tm1.1Eml

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

The dominant negative MitfMi allele restores retinal development in the Vsx2 mutants

vision/eye
• substantial improvements in eye size, tissue histology and retinal neurogenesis compared to mice homozygous for Vsx2tm2.1Eml alone
• substantial improvements in eye size compared to mice homozygous for Vsx2tm1.1Eml alone