Analysis Tools
mortality/aging
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• ~20% of mice succumb to death due to severe hydrocephalus around weaning
• however, remaining mice survive to adulthood without gross abnormalities
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growth/size/body
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• significant loss of multicilia in the nasal epithelium of adult mice
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craniofacial
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• significant loss of multicilia in the nasal epithelium of adult mice
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• conspicuously domed head in ~20% of mice with severe hydrocephalus around weaning
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respiratory system
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• TEM analysis of adult tracheas revealed that 48-83% of basal bodies remain undocked in the cytoplasm of multiciliated cells, with only a few cilia; in addition, cilia are frequently shortened
• when P8 tracheas are cultured ex vivo in the presence of taxol (a microtubule-stabilizing agent), only 35% of cytoplasmic basal bodies are attached to ciliary vesicles versus 68% in control tracheas
• in primary cultures of mouse tracheal epithelial cells (MTECs), multiciliated cells extend short and stubby cilia at 14 days after air-liquid interface induction (ALId14) with low-serum media
• at ALId14, the number of stage IV (axonemal elongation) multiciliated cells is decreased whereas the number of early stage multiciliated cells is increased; most stage IV multiciliated cells extend only short and scarce cilia
• at ALId14, only about 4.9% of total cells appear fully ciliated with abundant cilia versus about 46.5% in control MTEC cultures, and many undocked cytoplasmic basal bodies are observed; basal body recruitment of Cby1 is reduced in ~65% of multiciliated cells while recruitment of FAM92A and FAM92B is reduced in 50-65% of cells
• at ALId14, distribution of ciliary membrane proteins is disturbed, whereas basal body localization of IFT88, IFT20, and CP110 in multiciliated cells is normal
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• significant reduction in the number of airway multicilia in tracheal and sinus sections from adult mice
• modest reduction (~10%) in the number of FOXJ1-positive multiciliated cells in primary MTEC cultures at ALId14
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• significant loss of multicilia in the nasal epithelium of adult mice
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• significant loss of multicilia in the trachea of adult mice
• in primary MTEC cultures, multiciliated cells show severe defects in ciliogenesis at 14 days after an air-liquid interface induction (ALId14)
• TEM analysis of adult tracheas revealed that 48-83% of basal bodies remain undocked in the cytoplasm of multiciliated cells, with only a few cilia; in addition, cilia are frequently shortened
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nervous system
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• significant disruptions in the organization of basal bodies at the apical surface of ependymal multiciliated cells
• basal body patch areas relative to total apical cell surface areas are significantly reduced
• displacement of the basal body patches from the cell center relative to the radius of the apical cell surface is significantly increased
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• significant reduction in the number of ependymal multicilia in the adult subventricular zone
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hydrocephaly
(
J:255142
)
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• ~20% of mice die around weaning due to severe hydrocephalus
• an additional ~20% exhibit mild hydrocephalus that self resolves later
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• enlarged lateral ventricular spaces in all adult mice examined
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• significant reduction in the number of ependymal multicilia in the adult subventricular zone
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reproductive system
 N |
• surprisingly, female mice are fertile despite a reduced multicilia number in the adult oviduct epithelium
(J:255142)
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 N |
• 2- to 4-month-old male mice exhibit no significant differences in testis weight or sperm motility relative to controls
(J:307614)
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• significant reduction in the number of multiciliated cells in the oviduct epithelium of adult mice
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• a minority of cauda epididymal sperm exhibit morphological defects such as detached heads and gaps between the midpiece and the principal piece
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• a minority of cauda epididymal sperm exhibit gaps between the midpiece and the principal piece
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• a minority of cauda epididymal sperm are headless
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• significant reduction in the number of late-stage germ cells
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azoospermia
(
J:255142
)
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• no mature sperm are detected in the epididymis at 3 months of age
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• 2- to 4-month-old males show a dramatic reduction in sperm number from the cauda epididymis
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• marked dilation of the rete testis in adult males
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• clogged seminiferous tubules are frequently observed near the rete testis in intact testes due to extensive sperm agglutination
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• in some seminiferous tubules, germ cells are completely depleted with only Sertoli cells present
(J:255142)
• clogged seminiferous tubules are frequently observed near the rete testis in intact testes due to extensive sperm agglutination
(J:307614)
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• non-progressive thinning of the seminiferous tubule epithelium at 2 and 6 months of age, indicating dysfunctional multicilia in the efferent ducts
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• significant increase in seminiferous tubule diameter at 2 and 6 months of age, non-progressive
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• significant increase in seminiferous tubule lumen diameter at 2 and 6 months of age, non-progressive
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• variable degrees of degenerative changes in the seminiferous tubules of adult testes
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• many sperm accumulate in the efferent ducts, unlike in control ducts
• although FoxJ1-positive immature cells are present, multicilia are barely detectable in the efferent duct epithelium
• sperm aggregation and agglutination are commonly observed in the lumen of efferent ducts
• apical localization of Cby1 and the transition zone marker NPHP1 is severely diminished, suggesting basal body docking defects
• TEM analysis revealed numerous undocked basal bodies in the cytoplasm of multiciliated cells in the efferent ducts
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• efferent ducts are dilated to varying degrees
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• many cauda epididymal tubules contain only a few sperm with abnormal fluid secretions
• often, a few tubules contain agglutinated spermatozoa
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• male mice are completely infertile
(J:255142)
(J:307614)
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• at 2 and 6 months of age, sperm accumulation and agglutination are commonly observed in the lumen of seminiferous tubules and efferent ducts, leading to blockage of sperm progression
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cellular
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• significant disruptions in the organization of basal bodies at the apical surface of ependymal multiciliated cells
• basal body patch areas relative to total apical cell surface areas are significantly reduced
• displacement of the basal body patches from the cell center relative to the radius of the apical cell surface is significantly increased
|
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• significant reduction in the number of ependymal multicilia in the adult subventricular zone
|
|
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• significant reduction in the number of multiciliated cells in the oviduct epithelium of adult mice
|
|
• TEM analysis of adult tracheas revealed that 48-83% of basal bodies remain undocked in the cytoplasm of multiciliated cells, with only a few cilia; in addition, cilia are frequently shortened
• when P8 tracheas are cultured ex vivo in the presence of taxol (a microtubule-stabilizing agent), only 35% of cytoplasmic basal bodies are attached to ciliary vesicles versus 68% in control tracheas
• in primary cultures of mouse tracheal epithelial cells (MTECs), multiciliated cells extend short and stubby cilia at 14 days after air-liquid interface induction (ALId14) with low-serum media
• at ALId14, the number of stage IV (axonemal elongation) multiciliated cells is decreased whereas the number of early stage multiciliated cells is increased; most stage IV multiciliated cells extend only short and scarce cilia
• at ALId14, only about 4.9% of total cells appear fully ciliated with abundant cilia versus about 46.5% in control MTEC cultures, and many undocked cytoplasmic basal bodies are observed; basal body recruitment of Cby1 is reduced in ~65% of multiciliated cells while recruitment of FAM92A and FAM92B is reduced in 50-65% of cells
• at ALId14, distribution of ciliary membrane proteins is disturbed, whereas basal body localization of IFT88, IFT20, and CP110 in multiciliated cells is normal
|
|
• significant reduction in the number of airway multicilia in tracheal and sinus sections from adult mice
• modest reduction (~10%) in the number of FOXJ1-positive multiciliated cells in primary MTEC cultures at ALId14
|
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• significant loss of multicilia in the nasal epithelium of adult mice
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|
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• a minority of cauda epididymal sperm exhibit morphological defects such as detached heads and gaps between the midpiece and the principal piece
|
|
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• a minority of cauda epididymal sperm exhibit gaps between the midpiece and the principal piece
|
|
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• a minority of cauda epididymal sperm are headless
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|
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• significant reduction in the number of late-stage germ cells
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azoospermia
(
J:255142
)
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• no mature sperm are detected in the epididymis at 3 months of age
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• 2- to 4-month-old males show a dramatic reduction in sperm number from the cauda epididymis
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skeleton
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• conspicuously domed head in ~20% of mice with severe hydrocephalus around weaning
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endocrine/exocrine glands
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• marked dilation of the rete testis in adult males
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|
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• clogged seminiferous tubules are frequently observed near the rete testis in intact testes due to extensive sperm agglutination
|
|
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• in some seminiferous tubules, germ cells are completely depleted with only Sertoli cells present
(J:255142)
• clogged seminiferous tubules are frequently observed near the rete testis in intact testes due to extensive sperm agglutination
(J:307614)
|
|
|
• non-progressive thinning of the seminiferous tubule epithelium at 2 and 6 months of age, indicating dysfunctional multicilia in the efferent ducts
|
|
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• significant increase in seminiferous tubule diameter at 2 and 6 months of age, non-progressive
|
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• significant increase in seminiferous tubule lumen diameter at 2 and 6 months of age, non-progressive
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• variable degrees of degenerative changes in the seminiferous tubules of adult testes
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taste/olfaction
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• significant loss of multicilia in the nasal epithelium of adult mice
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