Mouse Genome Informatics
involves: 129P2/OlaHsd
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
• all die within 18 hours after birth, presumably from respiratory failure or dehydration (J:71611)
• all mice die within 24 hours of birth and most within 14 hour of birth (J:141730)

• levels of HMG-CoA reductase protein are reduced
• 30- to 40-fold elevation in 7-dehydrocholesterol (7DHC) levels in the brain and liver
• 7-dehydrodesmosterol is accumulated in the brain whereas desmosterol is not detected
• decrease in total sterol levels in the brain and liver
• decrease in cholesterol levels in the brain
• decrease in cholesterol levels in liver
• HMG-CoA reductase activities are reduced 6-fold in the liver and 2.7-fold in brain microsomes

respiratory system
• compact lungs with sparse, unconnected air spaces
• lungs of newborns are similar in appearance to normal 15- to 16-gestational day mice, suggesting that lungs may be immature
• at E19.5, saccular formation is absent with the failure of pre-alveolar septae thinning and development of sac spaces unlike in wild-type mice

• none of the pups suckle
• lack movement shortly after birth

• 12% exhibit cleft palate

renal/urinary system
• 90% exhibit greatly distended urinary bladder

• 12% exhibit cleft palate

digestive/alimentary system
• 12% exhibit cleft palate

liver/biliary system
• decrease in cholesterol levels in liver

nervous system
• decrease in cholesterol levels in the brain

Mouse Models of Human Disease
Smith-Lemli-Opitz Syndrome; SLOS 270400 J:71611