Mouse Genome Informatics
hm
    Dhcr7tm1Fdp/Dhcr7tm1Fdp
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygotes die during their first day of life, most probably as a result of their failure to feed

behavior/neurological
• homozygous mutant pups fail to suckle, as shown by absence of milk in their stomachs
• 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
• mutant pups exhibit general weakness in the absence of gross limb, skeletal, renal, adrenal or CNS abnormalities
• 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
• mutant newborns never vocalize alarm

homeostasis/metabolism
• mutant newborns with no nasal openings display cyanotic episodes consistent with obligate nasal breathing
• 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)
• mutant pups exhibit significantly reduced cholesterol levels in serum, cortex, midbrain, kidney, liver and muscle relative to wild-type pups

craniofacial
• 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
• 30% of mutant pups retain a nasal plug in an otherwise normally formed nose
• 9% of mutant pups lack an identifiable nasal opening

growth/size
• 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
• 30% of mutant pups retain a nasal plug in an otherwise normally formed nose
• 9% of mutant pups lack an identifiable nasal opening
• at birth, the average weight for mutant pups is 1.11 ▒ 0.10 g vs 1.44 ▒ 0.18 g for wild-type pups
• homozygotes exhibit intra-uterine growth retardation which becomes more pronounced during the last 2 days of gestation

respiratory system
• 30% of mutant pups retain a nasal plug in an otherwise normally formed nose
• 9% of mutant pups lack an identifiable nasal opening
• 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
• mutant lungs display diffuse alveolar atelectasis

nervous system
• mutant brains are small, but brain weights are proportional to body weight and show no increased apoptosis
• 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 ÁM) is significantly reduced
• impaired glutamate response does not appear to be due to altered expression of glutamate receptor subunits in mutant cortex

renal/urinary system
• mutant pups display a dilated bladder with meconium detected in the colon

digestive/alimentary system
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Smith-Lemli-Opitz Syndrome; SLOS 270400 J:68084 , J:165301