All Phenotypes App<tm1Dbo> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

App^tm1Dbo
targeted mutation 1, David R Borchelt
MGI:2136847

Summary

10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	App^tm1Dbo/App^tm1Dbo	involves: 129S7/SvEvBrd * C57BL/6J	MGI:2174917
cx2	App^tm1Dbo/App^tm1Dbo Npc1^m1N/Npc1^m1N	C.Cg-App^tm1Dbo Npc1^m1N	MGI:5305067
cx3	App^tm1Dbo/App⁺ Dab1^tm1Bwh/Dab1^tm1Bwh	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6	MGI:3810281
cx4	App^tm1Dbo/App^tm1Dbo Dab1^tm1Bwh/Dab1^tm1Bwh	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6	MGI:3810280
cx5	App^tm1Dbo/App⁺ Lrp4^tm1Her/Lrp4^tm1Her	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J	MGI:5561077
cx6	App^tm1Dbo/App^tm1Dbo Lrp4^tm1Her/Lrp4⁺	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J	MGI:5561078
cx7	App^tm1Dbo/App^tm1Dbo Lrp4^tm1Her/Lrp4^tm1Her	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J	MGI:5561079
cx8	Aplp2^tm1Dbo/Aplp2^tm1Dbo App^tm1Dbo/App^tm1Dbo	involves: 129S7/SvEvBrd * C57BL/6J	MGI:2176993
cx9	Aplp2^tm1Dbo/Aplp2^tm1Dbo App^tm1Dbo/App^tm1Dbo	involves: 129/Sv * 129X1/SvJ * C57BL/6	MGI:4847597
cx10	Aplp2^tm1Dbo/Aplp2^tm1Dbo App^tm1Dbo/App^tm3.1Zhe	involves: 129/Sv * 129X1/SvJ * C57BL/6	MGI:4847596

Allelic Composition	App^tm1Dbo/App^tm1Dbo
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
App^tm1Dbo mutation (4 available); any App mutation (89 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

abnormal active avoidance behavior ( J:53824 )

• age-related impairment in conditioned avoidance tests, seen at 10 months of age, but not at 4 months of age

abnormal spatial learning ( J:53824 )

• impairment in watermaze test of spatial learning, both at 4 and 10 months of age

decreased grip strength ( J:25512 )

• significantly reduced grip strength

abnormal locomotor activation ( J:25512 )

• decreased locomotor activity

decreased locomotor activity ( J:53824 )

cardiovascular system

hematoma ( J:241632 )

• hematomas are smaller following experimentally induced intracerebral hemorrhage as compared to wild-type, but are larger than homozygous App^tm1.1Wevn mice

intracerebral hemorrhage ( J:241632 )

• hematomas are smaller following experimentally induced intracerebral hemorrhage as compared to wild-type, but are larger than homozygous App^tm1.1Wevn mice

homeostasis/metabolism

increased susceptibility to induced thrombosis ( J:241632 )

• time to cessation of blood flow following induced carotid artery thrombosis is decreased as compared to wild-type and homozygous App^tm1.1Wevn mice

nervous system

intracerebral hemorrhage ( J:241632 )

• hematomas are smaller following experimentally induced intracerebral hemorrhage as compared to wild-type, but are larger than homozygous App^tm1.1Wevn mice

gliosis ( J:25512 )

• 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

astrocytosis ( J:53824 )

• reactive astrocytosis in many brain areas, but predominantly in the cortex and hippocampus at 14 weeks of age

abnormal neuron morphology ( J:53824 )

• 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

abnormal long-term potentiation ( J:53824 )

• impairment of ability of high frequency stimuli to induce LTP which correlated with extent of gliosis in stratum radiatum

growth/size/body

decreased body weight ( J:25512 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:53824

Allelic Composition	App^tm1Dbo/App^tm1Dbo Npc1^m1N/Npc1^m1N
Genetic Background	C.Cg-App^tm1Dbo Npc1^m1N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
App^tm1Dbo mutation (4 available); any App mutation (89 available)
Npc1^m1N mutation (3 available); any Npc1 mutation (72 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:172769 )

• mutants start to die at 50 days of age

growth/size/body

weight loss ( J:172769 )

• 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

increased brain cholesterol level ( J:172769 )

• 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

decreased brain size ( J:172769 )

Purkinje cell degeneration ( J:172769 )

• lower number of surviving Purkinje cells in cerebellar lobes VIII and X

astrocytosis ( J:172769 )

• mutants exhibit a greater increase in astrocytosis and microglia activation than in single Npc1 homozygotes

demyelination ( J:172769 )

• mutants exhibit demyelination in the white matter

behavior/neurological

impaired coordination ( J:172769 )

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

homeostasis/metabolism

increased brain cholesterol level ( J:172769 )

• 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 Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease	DOID:10652		J:172769
Niemann-Pick disease	DOID:14504		J:172769

Allelic Composition	App^tm1Dbo/App⁺ Dab1^tm1Bwh/Dab1^tm1Bwh
Genetic Background	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
App^tm1Dbo mutation (4 available); any App mutation (89 available)
Dab1^tm1Bwh mutation (0 available); any Dab1 mutation (77 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

small cerebellum ( J:132599 )

• the cerebellum volume is not as small as in Dab1^tm1Bwh homozygotes

Allelic Composition	App^tm1Dbo/App^tm1Dbo Dab1^tm1Bwh/Dab1^tm1Bwh
Genetic Background	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6

Find Mice

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

small cerebellum ( J:132599 )

• the cerebellum volume is not as small as in Dab1^tm1Bwh homozygotes

Allelic Composition	App^tm1Dbo/App⁺ Lrp4^tm1Her/Lrp4^tm1Her
Genetic Background	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
App^tm1Dbo mutation (4 available); any App mutation (89 available)
Lrp4^tm1Her mutation (1 available); any Lrp4 mutation (97 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:207796 )

• 20 of 49 mice die within 5 months

Allelic Composition	App^tm1Dbo/App^tm1Dbo Lrp4^tm1Her/Lrp4⁺
Genetic Background	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J

Find Mice

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:207796 )

• 6 of 45 mice die within 5 months

Allelic Composition	App^tm1Dbo/App^tm1Dbo Lrp4^tm1Her/Lrp4^tm1Her
Genetic Background	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J

Find Mice

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

preweaning lethality, incomplete penetrance ( J:207796 )

• despite Mendelian ratios at E18.5, fewer than expected mice are present at weaning

nervous system

abnormal neuron differentiation ( J:207796 )

• increased nerve terminal sprouting

abnormal neuromuscular synapse morphology ( J:207796 )

• reduced size and density of acetylcholine clusters compared with either single homozygote

cellular

abnormal neuron differentiation ( J:207796 )

• increased nerve terminal sprouting

Allelic Composition	Aplp2^tm1Dbo/Aplp2^tm1Dbo App^tm1Dbo/App^tm1Dbo
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aplp2^tm1Dbo mutation (1 available); any Aplp2 mutation (30 available)
App^tm1Dbo mutation (4 available); any App mutation (89 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

postnatal lethality, incomplete penetrance ( J:45851 )

• 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

reduced fertility ( J:45851 )

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

behavior/neurological

absent gastric milk in neonates ( J:45851 )

• 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

impaired righting response ( J:45851 )

ataxia ( J:45851 )

weakness ( J:45851 )

• 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

head tilt ( J:45851 )

spinning ( J:45851 )

growth/size/body

decreased body size ( J:45851 )

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

integument

pallor ( J:45851 )

• become pale by 12-36 hours after birth

nervous system

abnormal neuromuscular synapse morphology ( J:207796 )

• at E14.5, acetylcholine receptor clusters are less robust compared to in control mice

• however, prepatterned acetylcholine receptors are distributed along the central region

Allelic Composition	Aplp2^tm1Dbo/Aplp2^tm1Dbo App^tm1Dbo/App^tm1Dbo
Genetic Background	involves: 129/Sv * 129X1/SvJ * C57BL/6

Find Mice

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

postnatal lethality, complete penetrance ( J:166379 )

• although born in Mendelian ratios, no mice survive to weaning

Allelic Composition	Aplp2^tm1Dbo/Aplp2^tm1Dbo App^tm1Dbo/App^tm3.1Zhe
Genetic Background	involves: 129/Sv * 129X1/SvJ * C57BL/6

Find Mice

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

postnatal lethality, incomplete penetrance ( J:166379 )

• although born in Mendelian ratios, few mice survive to adulthood

nervous system

abnormal neuromuscular synapse morphology ( J:166379 )

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

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