Mouse Genome Informatics
involves: 129T2/SvEms * C57BL/6J
phenotype observed in females
phenotype observed in males
N normal phenotype
• pups die soon after birth (6-12 hours)

• body weight of pups is 73% of wild-type

• pups fail to feed
• pups are hypoactive

• lack morphologically intact peroxisomes
• structure of mitochondria is abnormal
• analysis of tissue and cultured skin fibroblasts indicate severe impairment of peroxisomal fatty acid oxidation and plasmalogen synthesis
• cultured cerebellar neurons exhibit a 40% decrease in mitochondrial dehydrogenase activity
• cultured cerebellar neurons from E19 mice show increased oxidative stress and apoptosis

endocrine/exocrine glands
• myelin-like lipid structures are seen in some adrenocortical cells

liver/biliary system
• hepatocytes exhibit an abundance of large lipid droplets

• severe hypotonia, with pups maintaining a contracted C posture

nervous system
• brains show disordered lamination in the cerebral cortex
• much of the cortical mantle is densely populated by degenerating neurons characterized by small, round, hyperchromatic nuclei, often with a thin rim of amphophilic cytoplasm

renal/urinary system
• podocyte foot processes are scarce
• delayed differentiation of glomeruli as evidenced by the reduced size and capillary structure and paucity of podocyte foot processes

respiratory system
• seen in a few rare cases

Mouse Models of Human Disease
Peroxisome Biogenesis Disorder 11a (zellweger); PBD11A 614883 J:84795