Mouse Genome Informatics
involves: 129S7/SvEvBrd * C57BL/6
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
• homozygotes survive to birth but die within a few hours of birth due to respiratory failure

• 92% (23 of 34) newborn homozygotes show delayed development of lower incisors
• 21.4% (6 of 28) newborn homozygotes lack a hard palate
• 15.8% (3 of 19) newborn homozygotes display a cleft secondary palate
• 6 of 34 newborn homozygotes lack lower incisors

• at E18.5, homozygotes are smaller than wild-type counterparts
• at E18.5, homozygotes weigh ~12% less than wild-type counterparts
• newborn homozygotes are growth retarded

• newborn homozygotes show decreased muscle mass in the diaphragmatic, pectoralis major and intercostal muscles
• however, no primary defects are observed as determined by analysis of ATPase activity, glycogen content and mitochondria

• in 4 of 28 homozygotes, one or both of the seventh ribs fail to fuse to the sternum
• in 61% (17 of 28) homozygotes, development of the thirteenth pair of ribs is limited
• Background Sensitivity: a higher percentage of homozygotes show limited formation of the thirteenth rib pair on an inbred 129/SvEv background than on a hybrid 129/SvEv x C57BL/6 background (81.8% vs 61%, respectively)
• in 28.6% (8 of 28) homozygotes, the thirteenth pair of ribs is absent
• all (28 of 28) newborn homozygotes have five lumbar vertebrae instead of six; only 2 of 15 wild-type controls show this defect

digestive/alimentary system
• 21.4% (6 of 28) newborn homozygotes lack a hard palate
• 15.8% (3 of 19) newborn homozygotes display a cleft secondary palate

• newborn homozygotes appear cyanotic

respiratory system
• newborn homozygotes fail to breathe
• mutant lungs are sank in liquid, and alveolar spaces appear poorly expanded, although no primary pulmonary defects are detected

• mutant whiskers are very thin and incorrectly oriented with shafts projecting parallel before turning perpendicularly
• newborns display a 25% increase in the stratum corneum cells relative to wild-type controls
• newborn homozygotes show a thickened granular and stratum corneum
• newborn homozygotes appear hypoxic (pale)
• newborn homozygotes display a shiny skin
• newborn homozygotes display a taut skin

Mouse Models of Human Disease
Restrictive Dermopathy, Lethal 275210 J:23925