Analysis Tools
mortality/aging
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• homozygotes die during their first day of life, most probably as a result of their failure to feed
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behavior/neurological
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• homozygous mutant pups fail to suckle, as shown by absence of milk in their stomachs
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• hand-fed mutant pups are able to swallow formula; however, their swallowing movements lack the typical rhythmic sucking/swallowing pattern observed in wild-type pups
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• mutant pups exhibit general weakness in the absence of gross limb, skeletal, renal, adrenal or CNS abnormalities
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• mutant pups exhibit hypotonia and decreased movement in the absence of gross limb or skeletal malformations
• hypotonia is already evident at birth and does not appear to be secondary to lack of feeding
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• mutant newborns never vocalize alarm
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homeostasis/metabolism
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• mutant newborns with no nasal openings display cyanotic episodes consistent with obligate nasal breathing
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• mutant pups display a 1678-fold increase in serum 7-dehydrocholesterol (7-DHC) levels relative to wild-type pups; in addition, tissue 7-DHC levels are elevated 250-, 265-, 250-, 791- and 2003-fold in cortex, midbrain, kidney, liver and muscle, respectively
(J:68084)
• 8-Dehydrocholesterol (an isomer of 7-DHC) is also markedly elevated in serum and similar tissue samples
(J:68084)
• 7-dehydrodesmosterol (7-DHD) is accumulated in brain whereas desmosterol levels are markedly reduced in the cortex and midbrain of mutant pups
(J:68084)
• 1-day old mice exhibit a striking localization of residual 7-dehydrocholesterol and cholesterol in the cerebellum and brainstem compared to wild-type mice that show diffuse cholesterol throughout the cerebellum, however normal localization of sterol metabolites is seen at E16-19
(J:165301)
• 7-dehydrocholesterol levels are about 8-fold higher in the cerebellum and brainstem than in controls
(J:165301)
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• mutant pups exhibit significantly reduced cholesterol levels in serum, cortex, midbrain, kidney, liver and muscle relative to wild-type pups
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craniofacial
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• 9% of mutant pups exhibit a cleft palate characterized by elevation of the palatal shelves but failure of the secondary palate to close in the midline
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• 30% of mutant pups retain a nasal plug in an otherwise normally formed nose
• 9% of mutant pups lack an identifiable nasal opening
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growth/size/body
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• 9% of mutant pups exhibit a cleft palate characterized by elevation of the palatal shelves but failure of the secondary palate to close in the midline
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• 30% of mutant pups retain a nasal plug in an otherwise normally formed nose
• 9% of mutant pups lack an identifiable nasal opening
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• at birth, the average weight for mutant pups is 1.11 0.10 g vs 1.44 0.18 g for wild-type pups
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• homozygotes exhibit intra-uterine growth retardation which becomes more pronounced during the last 2 days of gestation
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respiratory system
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• 30% of mutant pups retain a nasal plug in an otherwise normally formed nose
• 9% of mutant pups lack an identifiable nasal opening
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atelectasis
(
J:68084
)
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• mutant lungs display diffuse alveolar atelectasis
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aspiration
(
J:68084
)
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• hand-feeding of mutant pups is precluded by aspiration, with dye-labeled formula staining the trachea, bronchi and lung parenchyma; however, no pharynx or trachea malformations are observed
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nervous system
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• mutant brains are small, but brain weights are proportional to body weight and show no increased apoptosis
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• mutant frontal cortex neurons show a normal response to the neurotransmitter gamma-amino-n-butyric acid (GABA); however, the response of these same neurons to exogenous glutamate (24 M) is significantly reduced
• impaired glutamate response does not appear to be due to altered expression of glutamate receptor subunits in mutant cortex
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renal/urinary system
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• mutant pups display a dilated bladder with meconium detected in the colon
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digestive/alimentary system
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• 9% of mutant pups exhibit a cleft palate characterized by elevation of the palatal shelves but failure of the secondary palate to close in the midline
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Smith-Lemli-Opitz syndrome | DOID:14692 |
OMIM:270400 |
J:68084 , J:165301 | |
