Phenotypes associated with this allele

• Allele Symbol: Rac1^tm1.1Djk
• Allele Name: targeted mutation 1.1, David J Kwiatkowski
• Allele ID: MGI:2663669
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rac1^tm1.1Djk/Rac1^tm1.1Djk	involves: 129S4/SvJae * C57BL/6	MGI:2663672
cn2	Rac1^tm1Djk/Rac1^tm1.1Djk Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:2663670
cn3	Rac1^tm1Djk/Rac1^tm1.1Djk Tg(Msx2-cre)5Rem/0	involves: 129S4/SvJae	MGI:3834607
cn4	Rac1^tm1Djk/Rac1^tm1.1Djk Tg(Myh6-cre/Esr1*)1Liao/0	involves: 129S4/SvJae * C57BL/6	MGI:3654330

Genotype
MGI:2663672

hm1

• Allelic Composition: Rac1^tm1.1Djk/Rac1^tm1.1Djk
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

mortality/aging

embryonic lethality between somite formation and embryo turning, complete penetrance ( J:83457 )

• no viable homozygous mutant embryos are found at E8.5 or later

Genotype
MGI:2663670

cn2

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1.1Djk; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

immune system

impaired neutrophil chemotaxis ( J:83457 )

• in vitro, mutant bone marrow neutrophils show a ~50% reduction in fMLP-induced chemotaxis relative to wild-type neutrophils both at 1 and 10 uM fMLP

• mutant neutrophils show a significant reduction in fMLP-induced F-actin formation, with a slower rate of actin polymerization relative to wild-type neutrophils

• however, both PMA- and fMLP-stimulated mutant bone marrow neutrophils exhibit normal superoxide production relative to wild-type neutrophils

decreased leukocyte cell number ( J:83457 )

• 3 hrs after induction of peritonitis by sodium periodate injection, circulating leukocyte counts are not significantly increased, unlike in wild-type controls

decreased neutrophil cell number ( J:83457 )

• 3 hrs after induction of peritonitis, only a small increase in peripheral neutrophil counts is observed, unlike in wild-type controls where circulating neutrophil counts are increased by >3-fold

impaired neutrophil recruitment ( J:83457 )

• 3 hrs after sodium periodate injection into the peritoneum, mutant mice exhibit a >50% reduction in neutrophil accumulation at the site of inflammation relative to wild-type controls

decreased acute inflammation ( J:83457 )

• 3 hrs after i.p. injection of sodium periodate, mutant mice display impaired neutrophil chemotaxis and in vivo recruitment to sites of acute inflammation relative to wild-type controls

hematopoietic system

impaired neutrophil chemotaxis ( J:83457 )

• in vitro, mutant bone marrow neutrophils show a ~50% reduction in fMLP-induced chemotaxis relative to wild-type neutrophils both at 1 and 10 uM fMLP

• mutant neutrophils show a significant reduction in fMLP-induced F-actin formation, with a slower rate of actin polymerization relative to wild-type neutrophils

• however, both PMA- and fMLP-stimulated mutant bone marrow neutrophils exhibit normal superoxide production relative to wild-type neutrophils

decreased leukocyte cell number ( J:83457 )

• 3 hrs after induction of peritonitis by sodium periodate injection, circulating leukocyte counts are not significantly increased, unlike in wild-type controls

decreased neutrophil cell number ( J:83457 )

• 3 hrs after induction of peritonitis, only a small increase in peripheral neutrophil counts is observed, unlike in wild-type controls where circulating neutrophil counts are increased by >3-fold

impaired neutrophil recruitment ( J:83457 )

• 3 hrs after sodium periodate injection into the peritoneum, mutant mice exhibit a >50% reduction in neutrophil accumulation at the site of inflammation relative to wild-type controls

cellular

impaired neutrophil chemotaxis ( J:83457 )

• in vitro, mutant bone marrow neutrophils show a ~50% reduction in fMLP-induced chemotaxis relative to wild-type neutrophils both at 1 and 10 uM fMLP

• mutant neutrophils show a significant reduction in fMLP-induced F-actin formation, with a slower rate of actin polymerization relative to wild-type neutrophils

• however, both PMA- and fMLP-stimulated mutant bone marrow neutrophils exhibit normal superoxide production relative to wild-type neutrophils

Genotype
MGI:3834607

cn3

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1.1Djk; Tg(Msx2-cre)5Rem/0
• Genetic Background: involves: 129S4/SvJae

limbs/digits/tail

short forelimb ( J:145305 )

• partial forelimb truncation

absent hindlimb ( J:145305 )

Genotype
MGI:3654330

cn4

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1.1Djk; Tg(Myh6-cre/Esr1*)1Liao/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

cellular

oxidative stress ( J:109582 )

• superoxide anion production is reduced in cardiac-specific Rac1-nulls compared to wild-type in response to angiotensin II (increase of 3.3-fold in wild-type, 2.1-fold in heterozygotes and only 1.2 fold in Rac1 nulls)

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:109582 )

• ASK1 and NF-kappaB activities are increased in wild-type and to a lesser extent in heterozygotes by angiotensin II, but not at all in null mice

increased NAD(P)H oxidase activity ( J:109582 )

• NADPH oxidase activity is increased to a greater extent in response to angiotensin II in wild-type than in heterozygotes or cardiac-specific Rac1 nulls

cardiovascular system

abnormal myocardium layer morphology ( J:109582 )

• 2 weeks after infusion of angiotensin II, hearts from cardiac-specific Rac1-deletion show reduced end-diastolic myocardial wall thickness

abnormal myocardial fiber morphology ( J:109582 )

• cross-sectional areas of cardiomyocytes in wild-type and Rac1 heterozygotes are increased in response to angiotensin II (300 and 270 um² vs 200 um² in untreated controls) but areas of cardiomyocytes from nulls show no change

cardiac hypertrophy ( J:109582 )

• 2 weeks after infusion of angiotensin II or saline, hearts from cardiac specific Rac1-deletion show less hypertrophy than wild-type or Rac1 heterozygotes

increased heart left ventricle weight ( J:109582 )

• angiotensin II increases left ventricular mass of wild-type and Rac1 heterozygotes by 184 and 160% respectively, while cardiac-specific Rac1 nulls have only a 123% increase

muscle

abnormal myocardium layer morphology ( J:109582 )

• 2 weeks after infusion of angiotensin II, hearts from cardiac-specific Rac1-deletion show reduced end-diastolic myocardial wall thickness

abnormal myocardial fiber morphology ( J:109582 )

• cross-sectional areas of cardiomyocytes in wild-type and Rac1 heterozygotes are increased in response to angiotensin II (300 and 270 um² vs 200 um² in untreated controls) but areas of cardiomyocytes from nulls show no change

growth/size/body

cardiac hypertrophy ( J:109582 )

• 2 weeks after infusion of angiotensin II or saline, hearts from cardiac specific Rac1-deletion show less hypertrophy than wild-type or Rac1 heterozygotes