Mouse Genome Informatics
hm1
    Sorl1tm1Tew/Sorl1tm1Tew
either: (involves: 129/SvEmcTer * BALB/c) or (involves: 129/SvEmcTer * C57BL/6N)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• homozygotes are viable and fertile with no change in overall APP levels; however, neuron associated Abeta levels and production of sAPP in the brain are increased at 10 months of age (J:101417)
• increase in levels of amyloid beta peptide in the brain

homeostasis/metabolism
• increase in levels of amyloid beta peptide in the brain


Mouse Genome Informatics
hm2
    Sorl1tm1Tew/Sorl1tm1Tew
involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• at 3, 6, and 12-14 months of age, mice do not distinguish between old and new objects in the object recognition test, exploring the new and familiar object equally
• although mutants learn a well as wild-type mice during the acquisition phase of the Morris water maze, during the probe phase, 3, 6, and 12-16 month old mutants, are unable to remember the target quadrant

homeostasis/metabolism
• amyloid beta immunoreactive dystrophic neurites in the hippocampus are seen at 6 months and in the neocortex at 12 months

nervous system
• amyloid beta immunoreactive dystrophic neurites in the hippocampus are seen at 6 months and in the neocortex at 12 months
• phosphorylated tau is seen in neurons of the lateral entorhinal cortex, the neocrotex, and the hippocampus at 3, 6, and 12 months of age; somatodendritic localization of phosphorylated tau is not observed
• decrease in the number of ChAT-positive neurons in the nucleus basalis of Meynert at 6 and 12-14 months of age and in the medial septum/diagonal band of Broca at 3 and 6 months but not at 12-14 months
• degeneration of cholinergic neurons


Mouse Genome Informatics
cx3
    Sorl1tm1Tew/Sorl1tm1Tew
Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129 * C3H/HeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• amyloid beta levels and amyloid plaque burden are increased at 4.5 and 6 months of age, but not at 12 months of age, compared to transgenic mice wild-type for Sorl1 suggesting an acceleration in accumulation of amyloid beta
• some of the largest differences in amyloid measures are detected in the cerebellum

homeostasis/metabolism
• amyloid beta levels and amyloid plaque burden are increased at 4.5 and 6 months of age, but not at 12 months of age, compared to transgenic mice wild-type for Sorl1 suggesting an acceleration in accumulation of amyloid beta
• some of the largest differences in amyloid measures are detected in the cerebellum

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:142501


Mouse Genome Informatics
cx4
    Sorl1tm1Tew/Sorl1tm1Tew
Tg(CMV-IgkvaD11)BCat/Tg(CMV-IgkvaD11)BCat

involves: 129 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• at 3 and 6 months of age, mice do not distinguish between old and new objects in the object recognition test
• at 12-14 months of age, however, the non-spatial memory deficit seen in the object recognition test disappears
• during the acquisition phase of the Morris water maze, 12 month old mutants do not learn as well as wild-type mice
• during the probe phase of the Morris water maze, 3, 6, and 12-14 month old mice are unable to remember the target quadrant

homeostasis/metabolism
• amyloid beta immunoreactive clusters in dystrophic neurites are seen to a similar extent in the hippocampus as in single Tg(CMV-IgkvaD11)BCat mice at 3 months of age, however by 6 months, the number of amyloid beta immunoreactive clusters is increased two-fold, but then is similar to single transgenics at 12-14 months of age, indicating acceleration of the amyloidogenic process

nervous system
• amyloid beta immunoreactive clusters in dystrophic neurites are seen to a similar extent in the hippocampus as in single Tg(CMV-IgkvaD11)BCat mice at 3 months of age, however by 6 months, the number of amyloid beta immunoreactive clusters is increased two-fold, but then is similar to single transgenics at 12-14 months of age, indicating acceleration of the amyloidogenic process
• phosphorylated tau is seen in neurons of the lateral entorhinal cortex, the neocortex and the hippocampus at 12-14 months of age, but not at earlier times; somatodendritic localization of phosphorylated tau is not observed
• mice show decreased numbers of ChAT-positive neurons only in the medial septum/diagonal band of Broca at 12-14 months of age
• normal numbers of ChAT-positive neurons are seen in the nucleus basalis of Meynert at 3, 6, and 12-14 months of age and in the medial septum/diagonal band of Broca at 3, and 6 months of age, indicating some protection from cholinergic neurodegeneration at early stages