Mouse Genome Informatics
hm1
    Gfaptm2Hgmn/Gfaptm2Hgmn
involves: 129S6/SvEvTac * 129S7/SvEvBrd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• weigh less than wild-type or heterozygotes

nervous system
• develop more Rosenthal fibers than heterozygotes


Mouse Genome Informatics
ht2
    Gfaptm2Hgmn/Gfap+
involves: 129S6/SvEvTac * 129S7/SvEvBrd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• exhibit a more significant difference in body weight than heterozygous Gfaptm1Hgmn mutants

nervous system
• show increased sensitivity to kainate induced-seizures, with 50% compared to 10% of wild-type developing severe seizures and increased lethality over wild-type
• exhibit iron accumulation in the hypertrophic astrocytes of the corpus callosum
• develop Rosenthal fibers, especially within the hippocampus, olfactory bulb, corpus callosum, and rostral extension, as well as in subpial, perivascular and periventricular regions
• exhibit more Rosenthal fibers than seen in heterozygous Gfaptm1Hgmn mutants
• Rosenthal fibers are apparent at the pial surfaces of the brainstem and ventral midbrain and forebrain as early as P7
• astrocytes appear hypertrophic in the above regions at 3 months of age

homeostasis/metabolism
• exhibit iron accumulation in the hypertrophic astrocytes of the corpus callosum

behavior/neurological
• show increased sensitivity to kainate induced-seizures, with 50% compared to 10% of wild-type developing severe seizures and increased lethality over wild-type

Mouse Models of Human Disease
OMIM IDRef(s)
Alexander Disease 203450 J:114689


Mouse Genome Informatics
cx3
    Gfaptm2Hgmn/Gfap+
Cryab/Hspb2tm1Wawr/Cryab/Hspb2tm1Wawr

involves: 129S4/SvJae * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice remain viable in Cryab-null background in contrast to Cryab-null, GFAP-overexpressing mice (J:146191)


Mouse Genome Informatics
cx4
    Cryab/Hspb2tm1Wawr/Cryab/Hspb2tm1Wawr
Gfaptm2Hgmn/Gfap+

involves: 129S4/SvJae * 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice remain viable in Cryab-null background in contrast to Cryab-null, GFAP-overexpressing mice (J:146191)


Mouse Genome Informatics
cx5
    Gfaptm2Hgmn/Gfap+
Tg(GFAP)10Mes/0
Tg(GFAP-CRYAB)141.6Mes/0

involves: 129S4/SvJae * 129S7/SvEvBrd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• all animals survive compared to Tg(GFAP-Cryab)141.6Mes-positive double mutants which die around 30 days of age (J:146191)

nervous system
• Rosenthal fibers are observed, but numbers are significantly less than in Gfaptm2Hgmn/+/Tg(GFAP)10Mes animals; both soluble and insoluble GFAP levels are reduced


Mouse Genome Informatics
cx6
    Gfaptm2Hgmn/Gfap+
Tg(GFAP)10Mes/0

involves: 129S6/SvEvTac * 129S7/SvEvBrd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• almost all die at around 30 days of age

nervous system
• two mutants exhibit seizure-like episodes before death
• at 24 days of age, exhibit increased Rosenthal fiber formation and higher levels of insoluble Gfap than either single mutant
• astrocytes are hypertrophied in the regions of brain that normally show high levels of Gfap expression

behavior/neurological
• two mutants exhibit seizure-like episodes before death

Mouse Models of Human Disease
OMIM IDRef(s)
Alexander Disease 203450 J:114689


Mouse Genome Informatics
cx7
    Gfaptm2Hgmn/Gfap+
Tg(GFAP-CRYAB)141.6Mes/0

involves: 129S7/SvEvBrd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• the stress response is reduced by 90% at 6 weeks compared to the stress response is reduced by 90% at 6 weeks compared Gfaptm2Hgmn/+/+ mice


Mouse Genome Informatics
cx8
    Gfaptm2Hgmn/Gfap+
Tg(GFAP)10Mes/0

involves: 129S7/SvEvBrd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all animals die by under 50 days of age (most die around 30 days)

nervous system
• Rosenthal fiber formation is observed

Mouse Models of Human Disease
OMIM IDRef(s)
Alexander Disease 203450 J:146191