Analysis Tools
mortality/aging
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• homozygous mutant pups are stillborn, though cardiac activity is detected just prior to birth
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growth/size/body
cleft palate
(
J:84450
)
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• 88% of neonatal mutant pups display a cleft palate, not observed in wild-type pups
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• mutant pups have an average birth weight of 1.10 0 .01 g relative to 1.38 0.12 for control pups
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• mutant pups are growth retarded at birth, indicating a delay in intrauterine growth
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• in mutant pups, liver size is relatively increased (7% of body weight compared with 4% in controls) in the absence of overt lysosomal accumulation in either liver or brain tissue
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craniofacial
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• mutant pups display calvarial defects
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• the mineralized part of the interparietal bone is hypoplastic
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• mutant pups display hypoplasia of the distal mandibular arch
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• hypoplasia of the distal mandible
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micrognathia
(
J:84450
)
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• all mutant pups exhibit micrognathia due to hypoplasia of the distal mandidublar arch
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• mutant pups display a narrow frontonasal process
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cleft palate
(
J:84450
)
|
• 88% of neonatal mutant pups display a cleft palate, not observed in wild-type pups
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limbs/digits/tail
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• mutant pups display autopod patterning defects
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• mutant pups show a variable bifurcation of the fourth medial phalanges of either the fore or hind limbs
• bifurcation of the fourth medial phalanges is noted in at least one limb, in 56% of mutant embryos but in none of 10 control embryos
• proximal phalangeal bones display a more rectangular shape while middle phalangeal bones appear hypoplastic
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polydactyly
(
J:84450
)
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• 32% of mutant pups display postaxial polydactyly of the forelimbs versus only 5% of littermate controls
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bowed radius
(
J:84450
)
bowed ulna
(
J:84450
)
bowed tibia
(
J:84450
)
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• mutant pups exhibit bowed tibia and fibia
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• mutant pups display limb patterning defects in both the proximal-distal as well as the preaxial-postaxial axes
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short limbs
(
J:84450
)
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• mutant pups exhibit short and malformed fore- and hind limbs
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kinked tail
(
J:84450
)
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• most mutant pups have kinked tails
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homeostasis/metabolism
skin edema
(
J:84450
)
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• mutant pups exhibit subcutaneous edema
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• mutant pups display a reduced glycogen level in the liver
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• at E18.5, mutant embryos exhibit significantly increased tissue and serum levels of lathosterol relative to wild-type or heterozygous embryos
• in mutant tissues lathosterol accounts for 39% (serum), 48% (cortex), 53% (midbrain), 62% (liver), 52% (kidney) or 55% (skeletal muscle) of total sterols, whereas in wild-type tissues lathosterol accounts for 0.1-1.1% of total sterols, with the highest fractions in cortex (0.9%) and midbrain (1.1%)
• in mutant liver tissue the fraction of lathosterol increases from 32% at E12.5 to 61% at E18.5 with a corresponding reduction in cholesterol levels
• in mutant brain tissue increased lathosterol and significantly decreased cholesterol levels are noted from E12.5 to E18.5
• in E18.5 mutant cortex tissue desmosterol levels are significantly decreased, along with a 35-fold increase in cholesta-7,24-diene-3beta-ol and a 63-fold accumulation of lathosterol
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• at E18.5, mutant embryos display significantly decreased tissue and serum cholesterol levels relative to wild-type or heterozygous embryos
• in older mutant embryos, reduced cholesterol levels probably represent a dilution of maternally-derived cholesterol from the yolk sac as endogenous synthesis leads to lathosterol accumulation
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• in mutant brain tissue significantly decreased cholesterol levels are noted from E12.5 to E18.5
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skeleton
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• mutant pups display calvarial defects
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• the mineralized part of the interparietal bone is hypoplastic
|
|
• mutant pups display hypoplasia of the distal mandibular arch
|
|
• hypoplasia of the distal mandible
|
micrognathia
(
J:84450
)
|
• all mutant pups exhibit micrognathia due to hypoplasia of the distal mandidublar arch
|
|
• mutant pups show a variable bifurcation of the fourth medial phalanges of either the fore or hind limbs
• bifurcation of the fourth medial phalanges is noted in at least one limb, in 56% of mutant embryos but in none of 10 control embryos
• proximal phalangeal bones display a more rectangular shape while middle phalangeal bones appear hypoplastic
|
bowed radius
(
J:84450
)
bowed ulna
(
J:84450
)
bowed tibia
(
J:84450
)
|
• mutant pups exhibit bowed tibia and fibia
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digestive/alimentary system
cleft palate
(
J:84450
)
|
• 88% of neonatal mutant pups display a cleft palate, not observed in wild-type pups
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• mutant pups display decreased zymogen granules in the pancreas
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respiratory system
atelectasis
(
J:84450
)
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• mutant pups display diffuse atelectasis in the lung
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adipose tissue
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• mutant pups show increased vacuolation in brown fat tissue
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endocrine/exocrine glands
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• mutant pups display decreased zymogen granules in the pancreas
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liver/biliary system
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• in mutant pups, liver size is relatively increased (7% of body weight compared with 4% in controls) in the absence of overt lysosomal accumulation in either liver or brain tissue
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• mutant pups display a reduced glycogen level in the liver
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cellular
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• when mutant mouse embryonic fibroblasts are grown in cholesterol deficient media, enlarged membrane-bound cytoplasmic vacuoles with lamellar inclusions are observed; these intracellular inclusions appear to be in lysosomes and are not found in control cell lines
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integument
skin edema
(
J:84450
)
|
• mutant pups exhibit subcutaneous edema
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nervous system
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• in mutant brain tissue significantly decreased cholesterol levels are noted from E12.5 to E18.5
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