A mouse model for Zellweger syndrome.
The cerebro-hepato-renal syndrome of Zellweger is a fatal inherited disease caused by deficient import of peroxisomal matrix proteins. The pathogenic mechanisms leading to extreme hypotonia, severe mental retardation and early death are unknown. We generated a Zellweger animal model through inactivation of the murine Pxr1 gene (formally known as Pex5) that encodes the import receptor for most peroxisomal matrix proteins. Pxr1-/- mice lacked morphologically identifiable peroxisomes and exhibited the typical biochemical abnormalities of Zellweger patients. They displayed intrauterine growth retardation, were severely hypotonic at birth and died within 72 hours. Analysis of the neocortex revealed impaired neuronal migration and maturation and extensive apoptotic death of neurons.
Baes
M
M
Laboratory of Clinical Chemistry, Kathlieke Universiteit Leuven, Belgium. myriam.baes@uz.kuleuven.ac.be
Gressens
P
P
Baumgart
E
E
Carmeliet
P
P
Casteels
M
M
Fransen
M
M
Evrard
P
P
Fahimi
D
D
Declercq
P E
PE
Collen
D
D
van Veldhoven
P P
PP
Mannaerts
G P
GP
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001483:Base Sequence; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers; D003643:Death; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000473:pathology / Q000502:physiology; D000074435:Peroxisome-Targeting Signal 1 Receptor; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D015211:Zellweger Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
D017931:DNA Primers; C000614264:PEX5 protein, human; D000074435:Peroxisome-Targeting Signal 1 Receptor; C000614265:Pex5 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D004247:DNA