Mouse Genome Informatics
hm1
    Pex13tm1.1Crne/Pex13tm1.1Crne
involves: 129T2/SvEms * C57BL/6J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• pups die soon after birth (6-12 hours)

growth/size/body
• body weight of pups is 73% of wild-type

behavior/neurological
• pups fail to feed
• pups are hypoactive

cellular
• 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

muscle
• 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
OMIM IDRef(s)
Peroxisome Biogenesis Disorder 11a (zellweger); PBD11A 614883 J:84795


Mouse Genome Informatics
cn2
    Pex13tm1Crne/Pex13tm1.1Crne
Tg(Nes-cre)1Kln/0

involves: 129T2/SvEms * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 70.5% of mice die by 5 weeks of age, while 29.5% of mice die between 9-26 weeks of age
• body weight at time of weaning and litter size impact survival of mutants

growth/size/body
• mice that die by 5 weeks of age exhibit a lower body weight than mice that survive to 9-26 weeks of age
• 29.5% of mice show post-weaning onset of weight loss and die between 9-26 weeks of age
• 70.5% of mice exhibit growth retardation during the pre-weaning period and die by 5 weeks of age

behavior/neurological
• mice at P20 exhibit a delay in the pattern of acquisition of the majority of tested behaviors (negative geotaxis, cliff avoidance, vibrissa placing, grasp reflex, hyperkinesias, crossed extensor, acceleration righting and bar holding) with gradual improvement, suggesting a delay rather than ablation of reflex development
• mice exhibit an inability to splay hind limbs when lifted by the tail
• 7 of 11 mice show impaired performance on the rotarod, which is still seen at P30

cellular
• by P15, migration of granule cells from the external granule layer through the molecular layer to the internal granule layer is delayed

homeostasis/metabolism
• very-long-chain-fatty acid levels (C26:0/C22:0 ratio) in the brain are normal, however the C24:0/C22:0 ratio is reduced by 40%
• levels of brain C16:0 and C18:0 plasmalogens are reduced 20- and 40-fold, respectively in the brain
• levels of liver C16:0 plasmalogens are elevated 3-fold and C18:0 plasmalogens are slight increased
• brain peroxisomal enzymes dihydroxyacetone phosphate acyltransferase (DHAP-AT) and alkyl-DHAP synthase are reduced
• 5-fold increase in liver DHAP-AT activity

nervous system
• by P15, migration of granule cells from the external granule layer through the molecular layer to the internal granule layer is delayed
• levels of brain C16:0 and C18:0 plasmalogens are reduced 20- and 40-fold, respectively in the brain
• formation of cerebellar layers is delayed
• at P20, mutants show only partial development of the declival, intercrural and uvular fissures and impaired cerebellum foliation persists beyond P20, until at least P30
• the external granule layer is thicker at P15 and still is more evident at P20, the internal granule layer is thinner at P20, and the molecular layer is thinner at P20 and P30
• mutants do not exhibit a distinct Purkinje cell monolayer and show only small dendritic processes without forming a main dendrite at P5
• at P10, Purkinje cell somata are not aligned in a strict monolayer and small dendritic processes and spines arise randomly
• total length of Purkinje cells is decreased at P15, P20, and P30
• at P10, Purkinje cells show two main dendritic processes, the degree of branching is irregular and less complex, and dendrites are not in parallel alignment
• thinner at P20 and P30
• some mutants at P10 lack the declival, intercrural and uvular fissures that develop in controls and show shallower intercrural, precentral, primary, and prepyramidal fissures
• by P15, the declival, intercrural and uvular fissures have still not formed in some mutants and P20 mutants show shallower declival, intercrural, uvular and posterolateral fissures
• reactive gliosis in the cerebellum, cortex, and brain stem

skeleton
• older mice exhibit a hunchback posture

Mouse Models of Human Disease
OMIM IDRef(s)
Peroxisome Biogenesis Disorder 11a (zellweger); PBD11A 614883 J:167578