Mouse Genome Informatics
hm1
    Psen1tm1Pcw/Psen1tm1Pcw
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes are present at the expected Mendelian frequencies from E8.5 to E18.5 but fail to survive beyond P1

embryogenesis
• at E11.5, mutant embryos display disrupted somite segment polarity
• failure of sclerotome condensation suggests that the identity of the caudal halves of each segment are not specified
• at E10-E18, mutant embryos are significantly smaller than wild-type embryos
• at E9.5, mutant embryos display irregularly-shaped somites along the entire length of the neural tube
• at E9.5, mutant embryos display absence of somites at the caudal most regions; some somites appear compressed and fused, lacking a symmetric segmentation pattern across the midline
• despite defective somite segmentation, specification of somitic cell lineages (i.e. sclerotome and dermomyotome) appears unaffected at E10.5

skeleton
• at E13.5, homozygotes show significant defects in the formation of the vertebral column and ribs
• at E15.5, homozygotes exhibit abnormal bending of the basioccipital bone; the angle formed between the basioccipital bone and the atlas is distorted
• at E13.5, homozygotes display defective rib development
• at E13.5, homozygotes display fusion of the vertebral rudiments
• by E15.5, mutants show a significantly reduced vertebral column with abnormal segmentation adjacent to the spinal cord and fusion of the dorsal arches
• at E11.5, mutant embryos fail to exhibit sclerotome intrasegmental condensation

nervous system
• at E11.5, all homozygotes exhibit hemorrhages beneath the primordial dura and leptomeninges, and in neural parenchyma; rare focal necrosis is observed
• at E11.5, all homozygotes exhibit hemorrhages within the ventricles; however, overall architecture and cellularity of the brain is preserved
• at E15.5, mutant DRG appear fused over multiple segments along the craniocaudal axis of the vertebral column

growth/size/body
• at E10-E18, mutant embryos are significantly smaller than wild-type embryos
• at E10-E18, mutant mice are significantly smaller than wild-type mice

limbs/digits/tail
• at E10-E18, mutant embryos exhibit a stubby tail

cardiovascular system
• at E11.5, all homozygotes exhibit hemorrhages beneath the primordial dura and leptomeninges, and in neural parenchyma; rare focal necrosis is observed
• at E11.5, all homozygotes exhibit hemorrhages within the ventricles; however, overall architecture and cellularity of the brain is preserved

craniofacial
• at E15.5, homozygotes exhibit abnormal bending of the basioccipital bone; the angle formed between the basioccipital bone and the atlas is distorted


Mouse Genome Informatics
ht2
    Psen1tm1Mpm/Psen1tm1Pcw
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• exhibit impaired hippocampus-dependent contextual fear learning at 3 months of age, showing reduced freezing behavior
• however, show normal cued fear learning, anxiety, motor coordination and shock threshold

nervous system
• exhibit a 35% decrease in the number of newborn cells in the dentate gyrus of 3-month old mutants, indicating impaired adult neurogenesis

cellular
• exhibit a 35% decrease in the number of newborn cells in the dentate gyrus of 3-month old mutants, indicating impaired adult neurogenesis

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:91277
Alzheimer Disease; AD 104300 J:91277


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