Mouse Genome Informatics
hm
    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
• remains open at E12 and in areas along the edges inversion of the pigment epithelium is seen
• 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

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)

Mouse Models of Human Disease
OMIM IDRef(s)
Albinism, Ocular, with Sensorineural Deafness 103470 J:30758
Tietz Syndrome 103500 J:30758
Waardenburg Syndrome, Type 2A; WS2A 193510 J:30758