Mouse Genome Informatics
cx1
    Gfaptm2Mes/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
cx2
    Del(9Hspb2-Cryab)1Wawr/Del(9Hspb2-Cryab)1Wawr
Tg(GFAP)10Mes/0

involves: 129S4/SvJae * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• one third of mice null for Cryab show survival to 100 days compared to Cryab-sufficient Tg(GFAP)10Mes mice which display <10% mortality at about 30 days of age; most animals die at about 30 days of age

growth/size/body
• mice show significantly decreased body weights at 6 weeks and three months relative to wild-type

nervous system
• by 3 months of age, animals show formation of ubiquinated astrocytic protein (Rosenthal fiber) aggregates in the hippocampus (dentate gyrus and near pial surface of superior colliculus)


Mouse Genome Informatics
cx3
    Del(9Hspb2-Cryab)1Wawr/Cryab+
Tg(GFAP)10Mes/0

involves: 129S4/SvJae * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• two thirds of mice null for Cryab show survival to 100 days compared to Cryab-sufficient Tg(GFAP)10Mes mice which display <10% mortality at about 30 days of age; around 30% of animals die at about 30 days of age


Mouse Genome Informatics
cx4
    Del(9Hspb2-Cryab)1Wawr/Del(9Hspb2-Cryab)1Wawr
Tg(GFAP)10Mes/0
Tg(GFAP-CRYAB)141.6Mes/0

involves: 129S4/SvJae * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• majority of animals (about 90%) survive to 3 months of age

growth/size/body
N
• mice show significantly increased body weights at 6 weeks and three months relative to Tg(GFAP)10Mes and Tg(GFAP)10/Tg(GFAP-Cryab)141.6Mes Cryab-null animals; weights are comparable to wild-type (J:146191)

nervous system
• Rosenthal fibers which outline astrocytic processes are present in mutants


Mouse Genome Informatics
cx5
    Gfaptm2Mes/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
cx6
    Gfaptm2Mes/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


Mouse Genome Informatics
cx7
    Tg(GFAP)10Mes/0
Tg(GFAP-CRYAB)141.6Mes/0

involves: 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
tg8
    Tg(GFAP)10Mes/0
involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• severely affected mice die around 14 days of age; less affected mice live for more than 1 year
• mice display <10% mortality at about 30 days of age

growth/size/body
• mice show significantly decreased body weights at 6 weeks and three months relative to wild-type

nervous system
• astrocytes are enlarged and contain large eosinophilic aggregations resembling Rosenthal fibers;

Mouse Models of Human Disease
OMIM IDRef(s)
Alexander Disease 203450 J:99256