Phenotypes associated with this allele

• Allele Symbol: Serpind1^tm1Moto
• Allele Name: targeted mutation 1, Toshio Matsumoto
• Allele ID: MGI:3713783
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Serpind1^tm1Moto/Serpind1^tm1Moto	B6.Cg-Serpind1^tm1Moto	MGI:3713845
ht2	Serpind1^tm1Moto/Serpind1^+	B6.Cg-Serpind1^tm1Moto	MGI:3713846
ht3	Serpind1^tm1Toll/Serpind1^tm1Moto	involves: 129X1/SvJ * C57BL/6 * CBA	MGI:3713847
cx4	Apoe^tm1Unc/Apoe^tm1Unc Serpind1^tm1Moto/Serpind1^+	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3713848

Genotype
MGI:3713845

hm1

• Allelic Composition: Serpind1^tm1Moto/Serpind1^tm1Moto
• Genetic Background: B6.Cg-Serpind1^tm1Moto

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

mortality/aging

embryonic lethality between somite formation and embryo turning, complete penetrance ( J:122173 )

• homozygotes show lethality at E6.5 to 8.5

Genotype
MGI:3713846

ht2

• Allelic Composition: Serpind1^tm1Moto/Serpind1⁺
• Genetic Background: B6.Cg-Serpind1^tm1Moto

cardiovascular system

vascular smooth muscle hyperplasia ( J:122173 )

• intimal hyperplasia due to increased cell proliferation is observed in cuff-injured mice

abnormal vascular wound healing ( J:122173 )

• 4 week-arterial cuff injury results in enhanced intimal and adventitial space; intima/media ratio and adventitia/media ratio are increased relative to wild-type mice

• with wire insertion injury, femoral arteries show significant neointimal hyperplasia and high intima/media ratio compared to wild-type mice

• abnormalities are ameliorated with purified human SERPIND1 supplementation in both cuff and wire injury models

• in cuff-injured femoral arteries, expression levels of vascular remodeling factors like chemokines, inflammatory cytokines and transcription factors are enhanced in the vascular wall of mutants compared to expression in cuff-injured wild-type mouse arteries

hematopoietic system

hematopoietic system phenotype ( J:122173 )

N • fibrinogen level, plasma antithrombin activity and prothrombin time are similar to wild-type mice

abnormal platelet aggregation ( J:122173 )

• ADP-induced platelet aggregatory threshold index value is markedly reduced relative to wild-type, with aggregation of platelets occurring at lower ADP concentrations in mutant mice

homeostasis/metabolism

abnormal vascular wound healing ( J:122173 )

• 4 week-arterial cuff injury results in enhanced intimal and adventitial space; intima/media ratio and adventitia/media ratio are increased relative to wild-type mice

• with wire insertion injury, femoral arteries show significant neointimal hyperplasia and high intima/media ratio compared to wild-type mice

• abnormalities are ameliorated with purified human SERPIND1 supplementation in both cuff and wire injury models

• in cuff-injured femoral arteries, expression levels of vascular remodeling factors like chemokines, inflammatory cytokines and transcription factors are enhanced in the vascular wall of mutants compared to expression in cuff-injured wild-type mouse arteries

abnormal platelet aggregation ( J:122173 )

• ADP-induced platelet aggregatory threshold index value is markedly reduced relative to wild-type, with aggregation of platelets occurring at lower ADP concentrations in mutant mice

increased susceptibility to induced thrombosis ( J:122173 )

• wire injury results in a higher incidence of arterial occlusion due to thrombosis (20%) than in wild-type mice (10% incidence)

• abnormalities are ameliorated with purified human SERPIND1 supplementation

muscle

vascular smooth muscle hyperplasia ( J:122173 )

• intimal hyperplasia due to increased cell proliferation is observed in cuff-injured mice

Genotype
MGI:3713847

ht3

• Allelic Composition: Serpind1^tm1Toll/Serpind1^tm1Moto
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA

mortality/aging

mortality/aging ( J:122173 )

N • mice are born at or close to the expected Mendelian frequency (~25%), compared to homozygotes for Serpind1^tm1Moto allele when heterozygotes for each Serpind1 allele are bred

Genotype
MGI:3713848

cx4

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Serpind1^tm1Moto/Serpind1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

cardiovascular system

atherosclerotic lesions ( J:122173 )

• atherosclerotic plaque area in the aortic root is significantly increased compared to Apoe-deficient, Serpind1-sufficient mice; lipid deposition and PAR-1-positive cells in the plaques are more prominently observed in aortic root of mutants

cellular

oxidative stress ( J:122173 )

• superoxide production in the aortic root is greater than in controls

homeostasis/metabolism

abnormal urine nucleoside level ( J:122173 )

• excretion levels of 8-hydorxy-2'-deoxyguanosine, a marker of oxidative stress-induced DNA damage, are higher in double mutants than in controls

renal/urinary system

abnormal urine nucleoside level ( J:122173 )

• excretion levels of 8-hydorxy-2'-deoxyguanosine, a marker of oxidative stress-induced DNA damage, are higher in double mutants than in controls