Analysis Tools
craniofacial
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• at P30, H&E-stained cross sections of mutant cochleas do not identify any pathological changes other than a reduced thickness of the bony labyrinth
• however, the planar orientation of outer hair cells is not altered in the organ of Corti
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mortality/aging
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• homozygotes show partial lethality between E10.5 and birth
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skeleton
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• at P30, H&E-stained cross sections of mutant cochleas do not identify any pathological changes other than a reduced thickness of the bony labyrinth
• however, the planar orientation of outer hair cells is not altered in the organ of Corti
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growth/size/body
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• surviving homozygotes are smaller than control littermates
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embryo
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• at E10.5, homozygotes show a slight increase in primary cilium length in embryonic mesenchyme relative to heterozygous controls
• in culture, serum-starved mutant MEFs show a slight increase in primary cilium length but normal ciliary localization of the Ttc26-interacting protein Ift46, a subunit of Intraflagellar Transport (IFT) complex B
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• homozygotes display patterning defects that are characteristic of reduced Hedgehog signaling
• analysis of the Hedgehog pathway in mutant cells indicates that the signaling defect lies downstream of the accumulation of Gli at the tip of the primary cilium, but upstream of the subsequent dissociation of Gli from its negative regulator, Sufu
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• at E10.5, homozygotes display an aberrant pattern of neuronal specification in the ventral neural tube based on the expression of three markers of neuronal cell types: the number of Foxa2+ cells is reduced, the Nkx2-2-expressing V3 interneurons are shifted to the ventromedial region, and the ventral edge of the Mnx1 (HB9)-expressing motoneuron area is located abnormally close to the ventral border of the neural tube
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limbs/digits/tail
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• all homozygotes display preaxial polydactyly
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hearing/vestibular/ear
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• at P30, H&E-stained cross sections of mutant cochleas do not identify any pathological changes other than a reduced thickness of the bony labyrinth
• however, the planar orientation of outer hair cells is not altered in the organ of Corti
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• at 3-4 weeks of age, homozygotes exhibit increased ABR thresholds when broadband click stimuli between 30 and 90 dB SPL are used
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• at 3-4 weeks of age, homozygotes display a hearing impairment of variable severity
• however, no signs of middle ear inflammation are observed at P60
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nervous system
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• at E10.5, homozygotes display an aberrant pattern of neuronal specification in the ventral neural tube based on the expression of three markers of neuronal cell types: the number of Foxa2+ cells is reduced, the Nkx2-2-expressing V3 interneurons are shifted to the ventromedial region, and the ventral edge of the Mnx1 (HB9)-expressing motoneuron area is located abnormally close to the ventral border of the neural tube
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• at E10.5, immunostaining of the lumbar neural tube using antibodies against the V3 progenitor marker Nkx2-2, the floor plate marker Foxa2, and the motor neuron protein Mnx1 (HB9), revealed reduced Foxa2 expression and ventralization of the Nkx2-2- and Mnx1(HB9)-expressing cells, indicating patterning defects that are typical of reduced Hedgehog signaling
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• at 1 year of age, homozygotes display a slightly thinner outer segment layer
• however, no significant photoreceptor degeneration is observed
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vision/eye
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• at 1 year of age, homozygotes display a slightly thinner outer segment layer
• however, no significant photoreceptor degeneration is observed
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• at 1 year of age, homozygotes display a slightly thinner retina relative to control littermates
• however, no retinopathy linked to primary cilium dysfunction is observed
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cellular
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• at E10.5, homozygotes show a slight increase in primary cilium length in embryonic mesenchyme relative to heterozygous controls
• in culture, serum-starved mutant MEFs show a slight increase in primary cilium length but normal ciliary localization of the Ttc26-interacting protein Ift46, a subunit of Intraflagellar Transport (IFT) complex B
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renal/urinary system
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• at 1 year of age, mutant kidneys appear histologically normal and lack cysts
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