Mouse Genome Informatics
hm1
    Apptm1Dbo/Apptm1Dbo
involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• age-related impairment in conditioned avoidance tests, seen at 10 months of age, but not at 4 months of age
• impairment in watermaze test of spatial learning, both at 4 and 10 months of age
• significantly reduced grip strength
• decreased locomotor activity

nervous system
• reactive gliosis was observed throughout the cortical layers of the neocortex and extensive astrogliosis was seen in the CA1 region of the hippocampus, however did not observe neuronal cell damage
• reactive astrocytosis in many brain areas, but predominantly in the cortex and hippocampus at 14 weeks of age
• the branching of dendrites of both cortical and hippocampal neurons was much less extensive, however did not show any loss of cells in the cortex or the hippocampus
• impairment of ability of high frequency stimuli to induce LTP which correlated with extent of gliosis in stratum radiatum

growth/size
• body weight was 15-20% less at all ages compared with that of controls

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:53824


Mouse Genome Informatics
cx2
    Apptm1Dbo/Apptm1Dbo
Npc1m1N/Npc1m1N

C.Cg-Apptm1Dbo Npc1m1N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants start to die at 50 days of age

growth/size
• mutants exhibit severe weight loss, with weight at 3 weeks of age lower than seen in single homozygous App mice, but then increases so that by 12 weeks of age, loss of body weight is similar to single Npc1 homozygotes

nervous system
• mutants exhibit a greater vesicular accumulation of and wider distribution of cholesterol in the cerebellum, the motor cortex, the hippocampus and dentate gyrus than single Npc1 homozygotes
• lower number of surviving Purkinje cells in cerebellar lobes VIII and X
• mutants exhibit a greater increase in astrocytosis and microglia activation than in single Npc1 homozygotes
• mutants exhibit demyelination in the white matter

behavior/neurological
• mutants exhibit an exacerbated motor coordination deficit than seen in single Npc1 homozygotes

homeostasis/metabolism
• mutants exhibit a greater vesicular accumulation of and wider distribution of cholesterol in the cerebellum, the motor cortex, the hippocampus and dentate gyrus than single Npc1 homozygotes


Mouse Genome Informatics
cx3
    Aplp2tm1Dbo/Aplp2tm1Dbo
Apptm1Dbo/Apptm3.1Zhe

involves: 129/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• although born in Mendelian ratios, few mice survive to adulthood

nervous system
• neuromuscular junction exhibit mislocalization of choline transporters and reduced synaptophysin staining compared with wild-type mice


Mouse Genome Informatics
cx4
    Aplp2tm1Dbo/Aplp2tm1Dbo
Apptm1Dbo/Apptm1Dbo

involves: 129/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• although born in Mendelian ratios, no mice survive to weaning


Mouse Genome Informatics
cx5
    Apptm1Dbo/Apptm1Dbo
Dab1tm1Bwh/Dab1tm1Bwh

involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• the cerebellum volume is not as small as in Dab1tm1Bwh homozygotes


Mouse Genome Informatics
cx6
    Apptm1Dbo/App+
Dab1tm1Bwh/Dab1tm1Bwh

involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• the cerebellum volume is not as small as in Dab1tm1Bwh homozygotes


Mouse Genome Informatics
cx7
    Apptm1Dbo/App+
Lrp4tm1Her/Lrp4tm1Her

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 20 of 49 mice die within 5 months


Mouse Genome Informatics
cx8
    Apptm1Dbo/Apptm1Dbo
Lrp4tm1Her/Lrp4+

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 6 of 45 mice die within 5 months


Mouse Genome Informatics
cx9
    Apptm1Dbo/Apptm1Dbo
Lrp4tm1Her/Lrp4tm1Her

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• despite Mendelian ratios at E18.5, fewer than expected mice are present at weaning

nervous system
• increased nerve terminal sprouting
• reduced size and density of acetylcholine clusters compared with either single homozygote

cellular
• increased nerve terminal sprouting


Mouse Genome Informatics
cx10
    Aplp2tm1Dbo/Aplp2tm1Dbo
Apptm1Dbo/Apptm1Dbo

involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• incomplete penetrance, 80% of mice die within one week of birth
• lethality is not due to cardiopulmonary function as the heart and lungs appeared normal

reproductive system
• no abnormalities in ovaries and testis, indicating that physiological or behavioral correlates, rather than anatomical aspects, are responsible for decrease in fertility

behavior/neurological
• most pups have little or no milk in stomach, however no lesions in the face, palate, esophagous, stomach, intestine, or colon were seen and cranial nerves implicated in feeding appeared normal
• by 12-36 hours after birth, double homozygous mice appear weaker, however mice exhibit normal muscle histology, abundant lower motor neurons in the ventral horn of spinal cords, and normal neuromuscular transmission

growth/size
• survivors lag behind in growth and are 20-30% smaller, even into adulthood, compared to controls

integument
• become pale by 12-36 hours after birth

nervous system
• at E14.5, acetylcholine receptor clusters are less robust compared to in control mice
• however, prepatterned acetylcholine receptors are distributed along the central region