Mouse Genome Informatics
hm1
    Psen2tm1Ber/Psen2tm1Ber
either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• interestingly, adult homozygotes are viable and display no discernible defects
• no abnormalities in somite segmentation or cardiac looping are observed at E8.5


Mouse Genome Informatics
cn2
    Psen1tm1Jzt/Psen1tm1Jzt
Psen2tm1Ber/Psen2tm1Ber
Tg(Camk2a-cre)T29-1Stl/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• by 10 months of age mutants have impaired performance in a novel object recognition test
• by 10 months of age some mutants show increased activity in an open field test

cellular
• a dramatic increase in apoptosis is seen in the degenerating forebrain

growth/size
• by 10 months of age mutant mice start to show reduced body weights compared to wild-type

nervous system
• the lateral ventricles are immensely enlarged compared to wild-type or single knockout mice
• the third ventricle is immensely enlarged compared to wild-type or single knockout mice
• the thickness of the corpus callosum is about a third that of controls
• the thickness of the molecular layers between the CA1 pyramidal cells and dentate gyrus is significantly reduced
• the cortex is about half the normal thickness and the 6 layers can no longer be distinguished
• increased Gfap expression indicates that reactive astrogliosis occurs along with forebrain degeneration
• changes in the expression of several markers indicate that neuronal atrophy occurs along with forebrain degeneration
• degeneration is seen in the forebrain

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 4 606889 J:90685
Alzheimer Disease; AD 104300 J:90685


Mouse Genome Informatics
cx3
    Psen1tm1Pcw/Psen1+
Psen2tm1Ber/Psen2+

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• double heterozygotes are viable and phenotypically normal


Mouse Genome Informatics
cx4
    Psen1tm1Pcw/Psen1+
Psen2tm1Ber/Psen2tm1Ber

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mutant mice are viable and phenotypically normal


Mouse Genome Informatics
cx5
    Psen1tm1Pcw/Psen1tm1Pcw
Psen2tm1Ber/Psen2tm1Ber

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• double homozygotes die at E9-E9.5 probably due to cardiovascular failure

embryogenesis
• at E8.5, double homozygotes display underdeveloped second branchial arches
• at E8.5, double homozygotes exhibit disorganization of the trunk paraxial mesoderm
• at E8.5, double homozygotes show a severe disorganization of the trunk ventral neural tube
• in some cases, the notochord is completely surrounded by disordered ventral neural tube cells
• at E8.5 and E9, double homozygotes display a delay in the closure of the anterior neuropore
• at E8.5-E9, double homozygotes exhibit a kinked neural tube
• at E8.5-E9, double homozygotes display abnormal somite segmentation
• at E9-E9.5, double homozygotes exhibit chorioallantoic fusion defects

nervous system
• at E8.5, double homozygotes show a severe disorganization of the trunk ventral neural tube
• in some cases, the notochord is completely surrounded by disordered ventral neural tube cells
• at E8.5 and E9, double homozygotes display a delay in the closure of the anterior neuropore
• at E8.5-E9, double homozygotes exhibit a kinked neural tube
• at E8.5 and E9, double homozygotes display loss of mesenchyme cells in the presumptive midbrain
• at E8.5, double homozygotes show an apparent expanded forebrain

cardiovascular system
• at E8.5 and E9, double homozygotes exhibit unlooped hearts

craniofacial
• at E8.5, double homozygotes display underdeveloped second branchial arches


Mouse Genome Informatics
cx6
    Psen1tm1Pcw/Psen1tm1Pcw
Psen2tm1Ber/Psen2+

involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant embryos die between E9.5 and E13.5

embryogenesis
• at E9, mutant embryos display underdeveloped second branchial arches
• at E8.5, mutant embryos show a severe disorganization of the trunk ventral neural tube
• at E9, mutant embryos display a delay in the closure of the anterior neuropore
• at E8.5-E9, mutant embryos display a variable phenotype, ranging from no somite segmentation to the formation of highly disorganized somites

nervous system
• at E8.5, mutant embryos show a severe disorganization of the trunk ventral neural tube
• at E9, mutant embryos display a delay in the closure of the anterior neuropore

cardiovascular system
• some mutant embryos exhibit heart looping delays at E8.5 and E9, whereas others show partial heart looping at E9

craniofacial
• at E9, mutant embryos display underdeveloped second branchial arches