Phenotypes associated with this allele

• Allele Symbol: Myh9^tm1.1Gac
• Allele Name: targeted mutation 1.1, Christian Gachet
• Allele ID: MGI:3843980
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Myh9^tm1.1Gac/Myh9^tm1.1Gac Tg(Pf4-icre)Q3Rsko/0	involves: 129 * C57BL/6	MGI:3844021
cn2	Myh9^tm1.1Gac/Myh9^+ Tg(Pf4-icre)Q3Rsko/0	involves: 129 * C57BL/6	MGI:3844022
cn3	Myh9^tm1.1Gac/Myh9^tm1.1Gac Tg(NPHS2-cre)295Lbh/0	involves: 129 * C57BL/6 * SJL	MGI:5432397

Genotype
MGI:3844021

cn1

• Allelic Composition: Myh9^tm1.1Gac/Myh9^tm1.1Gac; Tg(Pf4-icre)Q3Rsko/0
• Genetic Background: involves: 129 * C57BL/6

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:148233 )

• during bleed time experiments, mice die within 20 minutes if not cauterized manually

hematopoietic system

abnormal platelet morphology ( J:148233 )

• platelets are twice the size as in wild-type mice

thrombocytopenia ( J:148233 )

• the number of platelets is 40% of wild-type

• however, in vitro platelet half-life is normal

abnormal platelet shape ( J:148233 )

• some ovoid platelets are mixed in with the normal population unlike in wild-type mice

• following activation with thrombin or U46619, platelets fail to undergo spheration unlike similarly treated wild-type platelets

• activated platelets exhibit very little shape change unlike wild-type platelets

abnormal platelet physiology ( J:148233 )

• platelets fail to exhibit retraction after thrombin activation unlike wild-type platelets

• at low concentrations of thrombin and U46619, platelets exhibit decreased aggregation compared to wild-type platelets

• following activation with thrombin or U46619, platelets fail to undergo spheration unlike similarly treated wild-type platelets

• serotonin release from dense granules is decreased after activation with U46619 or low concentrations of thrombin compared to similarly treated wild-type platelets

• activated platelets exhibit very little shape change unlike wild-type platelets

• activated platelets fail to form stress fibers unlike wild-type platelets

• however, platelet aggregation does occur

homeostasis/metabolism

abnormal blood coagulation ( J:148233 )

• in vitro under flow conditions and in vivo, thrombus organization is impaired compared to in wild-type mice

abnormal platelet physiology ( J:148233 )

• platelets fail to exhibit retraction after thrombin activation unlike wild-type platelets

• at low concentrations of thrombin and U46619, platelets exhibit decreased aggregation compared to wild-type platelets

• following activation with thrombin or U46619, platelets fail to undergo spheration unlike similarly treated wild-type platelets

• serotonin release from dense granules is decreased after activation with U46619 or low concentrations of thrombin compared to similarly treated wild-type platelets

• activated platelets exhibit very little shape change unlike wild-type platelets

• activated platelets fail to form stress fibers unlike wild-type platelets

• however, platelet aggregation does occur

increased bleeding time ( J:148233 )

• mice exhibit increased bleed time compared with wild-type mice

• during bleed time experiments, mice die within 20 minutes if not cauterized manually

Genotype
MGI:3844022

cn2

• Allelic Composition: Myh9^tm1.1Gac/Myh9⁺; Tg(Pf4-icre)Q3Rsko/0
• Genetic Background: involves: 129 * C57BL/6

hematopoietic system

abnormal platelet physiology ( J:148233 )

• platelets exhibit decreased retraction after thrombin activation compared to wild-type platelets

homeostasis/metabolism

abnormal platelet physiology ( J:148233 )

• platelets exhibit decreased retraction after thrombin activation compared to wild-type platelets

Genotype
MGI:5432397

cn3

• Allelic Composition: Myh9^tm1.1Gac/Myh9^tm1.1Gac; Tg(NPHS2-cre)295Lbh/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

renal/urinary system

renal/urinary system phenotype ( J:173971 )

N • surprisingly, mice are viable and do not develop overt chronic kidney disease up to 9 months of age

N • no excessive proteinuria at 1-9 months of age relative to control mice

N • normal urine albumin/creatinine ratios at 3-9 months of age relative to control mice

albuminuria ( J:173971 )

• at 3, 4, and 6 weeks after adriamycin injection, mice develop significantly more albuminuria than similarly-treated control mice

fused podocyte foot processes ( J:173971 )

• after adriamycin injection, mice exhibit patches of foot process fusion, unlike similarly-treated control mice

podocyte foot process effacement ( J:173971 )

• after adriamycin injection, mice exhibit patches of severe foot process effacement, unlike similarly-treated control mice

podocyte microvillus transformation ( J:173971 )

• after adriamycin injection, mice exhibit evidence of pseudovillous transformation, unlike similarly-treated control mice

increased renal glomerulus basement membrane thickness ( J:173971 )

• after adriamycin injection, mice exhibit thickening of the basement membrane in some glomerular loops, unlike similarly-treated control mice

glomerulosclerosis ( J:173971 )

• at 6 weeks after adriamycin injection, mice develop focal and segmental glomerulosclerosis ranging from mild segmental sclerosis to severe global sclerosis, unlike similarly-treated control mice which develop foci of mild sclerosis but no globally sclerotic glomeruli

renal cast ( J:173971 )

• at 6 weeks after adriamycin injection, mice exhibit numerous proteinaceous casts, unlike similarly-treated control mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:173971 )

N • no excessive proteinuria at 1-9 months of age relative to control mice

N • normal urine albumin/creatinine ratios at 3-9 months of age relative to control mice

N • normal serum creatinine and BUN levels at 9 months of age relative to control mice

albuminuria ( J:173971 )

• at 3, 4, and 6 weeks after adriamycin injection, mice develop significantly more albuminuria than similarly-treated control mice

increased susceptibility to injury ( J:173971 )

• following injection with doxorubicin hydrochloride (adriamycin; 15 ug/g) to induce kidney podocyte injury, 9-11 month old mice develop severe proteinuria and glomerulosclerosis, unlike similarly-treated control mice

growth/size/body

growth/size/body region phenotype ( J:173971 )

N • normal body weight at 9 months of age relative to control mice

cardiovascular system

cardiovascular system phenotype ( J:173971 )

N • no significant difference in tail cuff blood pressure at 11-12 months of age relative to control mice