Phenotypes associated with this allele

• Allele Symbol: Rac1^tm1Djk
• Allele Name: targeted mutation 1, David J Kwiatkowski
• Allele ID: MGI:2663662
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Rac1^tm1Djk/Rac1^tm1Djk Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor^+ Tg(Mef2c-cre)2Blk/0	involves: 129 * BALB/c * C57BL/6 * C57BL/6J	MGI:7545527
cn2	Rac1^tm1Djk/Rac1^tm1.1Djk Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:2663670
cn3	Grhl3^tm1(cre)Cgh/Grhl3^+ Gt(ROSA)26Sor^tm1(ptxA)Cgh/Gt(ROSA)26Sor^+ Rac1^tm1Djk/Rac1^tm1Djk	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * SJL	MGI:4438086
cn4	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Rac1^tm1Djk/Rac1^+ Tg(Msx2-cre)5Rem/0	involves: 129S4/SvJae	MGI:3834608
cn5	Rac1^tm1Djk/Rac1^tm1.1Djk Tg(Msx2-cre)5Rem/0	involves: 129S4/SvJae	MGI:3834607
cn6	Gt(ROSA)26Sor^tm1(Dkk1)Flng/Gt(ROSA)26Sor^+ Rac1^tm1Djk/Rac1^+ Tg(Msx2-cre)5Rem/0	involves: 129S4/SvJae * 129X1/SvJ	MGI:3834606
cn7	Rac1^tm1Djk/Rac1^tm1Djk Tg(Mef2c-cre)2Blk/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:7545526
cn8	Rac1^tm1Djk/Rac1^tm1Djk Tg(Nkx2-5-cre)9Eno/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:7545224
cn9	Rac1^tm1Djk/Rac1^tm1Djk Tg(Pf4-icre)Q3Rsko/0	involves: 129S4/SvJae * C57BL/6	MGI:6107686
cn10	Rac1^tm1Djk/Rac1^tm1.1Djk Tg(Myh6-cre/Esr1*)1Liao/0	involves: 129S4/SvJae * C57BL/6	MGI:3654330
cn11	Rac1^tm1Djk/Rac1^tm1Djk Tg(KRT14-cre/ERT)20Efu/0	involves: 129S4/SvJae * C57BL/6 * CD-1	MGI:3607402

Genotype
MGI:7545527

cn1

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1Djk; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺; Tg(Mef2c-cre)2Blk/0
• Genetic Background: involves: 129 * BALB/c * C57BL/6 * C57BL/6J

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

cardiovascular system

abnormal interventricular septum muscular part morphology ( J:315097 )

• at E11.5, hearts show deficient second heart field (SHF) contribution to the developing muscular interventricular septum between the right (RV) and left ventricle (LV)

• at E12.5 and E15.5, the interventricular septum has a major deficiency of SHF-derived cells, leading to formation of a bifid cardiac apex

cellular

decreased cell migration ( J:315097 )

• E12.5 right ventricle (RV) explant cultures exhibit only non-SHF-derived (mT-labeled) cells migrating from the RV explant by day 6 and very few to no SHF-derived (mG-labeled) cell migration

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:4438086

cn3

• Allelic Composition: Grhl3^tm1(cre)Cgh/Grhl3⁺; Gt(ROSA)26Sor^tm1(ptxA)Cgh/Gt(ROSA)26Sor⁺; Rac1^tm1Djk/Rac1^tm1Djk
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * SJL

embryo

spina bifida ( J:157446 )

• observed in about 58% of viable embryos collected at 14.5 days post coitus

• folate injections performed on pregnant females does not affect penetrance

nervous system

spina bifida ( J:157446 )

• observed in about 58% of viable embryos collected at 14.5 days post coitus

• folate injections performed on pregnant females does not affect penetrance

exencephaly ( J:157446 )

• observed with around 83% frequency in viable embryos collected at 14.5 days post coitus

• folate injections performed on pregnant females does not affect penetrance

Genotype
MGI:3834608

cn4

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Rac1^tm1Djk/Rac1⁺; Tg(Msx2-cre)5Rem/0
• Genetic Background: involves: 129S4/SvJae

limbs/digits/tail

abnormal forelimb morphology ( J:145305 )

• most forelimbs lack structures distal to the scapula

absent hindlimb ( J:145305 )

Genotype
MGI:3834607

cn5

• 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:3834606

cn6

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Dkk1)Flng}/Gt(ROSA)26Sor⁺; Rac1^tm1Djk/Rac1⁺; Tg(Msx2-cre)5Rem/0
• Genetic Background: involves: 129S4/SvJae * 129X1/SvJ

limbs/digits/tail

short forelimb ( J:145305 )

• severe forelimb truncation

absent hindlimb ( J:145305 )

Genotype
MGI:7545526

cn7

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1Djk; Tg(Mef2c-cre)2Blk/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

mortality/aging

perinatal lethality, incomplete penetrance ( J:315097 )

• seven of 28 mice collected at P0 at dead

cardiovascular system

abnormal ventricle myocardium morphology ( J:315097 )

• at P0, the right ventricle (RV) myocardium shows an absence of long F-actin filaments

• at E13.5, active (non-phosphorylated) beta-catenin staining between cell junctions is decreased in the RV myocardium

• at E13.5, mRNA levels of several transcription factors involved in heart development (Gata4, Nkx2.5, Tbx5 and Hand2) are significantly decreased in the RV myocardium

• however, Tbx20 mRNA levels are normal in the RV at E13.5

trabecula carnea hypoplasia ( J:315097 )

• at P0, the right ventricle (RV) myocardium shows poor trabeculation

thin right ventricle myocardium compact layer ( J:315097 )

• at P0, the RV compact myocardium is significantly thinner than in control hearts

abnormal fetal cardiomyocyte morphology ( J:315097 )

• at P0, RV cardiomyocytes appear rounded (spherically shaped) and exhibit defective polarity with loss of long F-actin filaments; active beta-catenin staining at cell-cell junctions is decreased at E13.5, suggesting reduced cell adhesion

• at E12.5 and E15.5, expression of SCRIB (scribble planar cell polarity protein) is almost absent in the RV and interventricular septum junction, supporting a failure of cardiomyocytes to undergo polarization

• in culture, neonatal cardiomyocytes show disrupted actin organization, absence of distinct cell projections, and a significantly shorter long-axis length; >40% of cardiomyocytes are rounded, whereas control cardiomyocytes are elongated

abnormal heart apex morphology ( J:315097 )

• at P0, all hearts (28 of 28) exhibit a deep interventricular groove and a bifurcation between the right (RV) and the left ventricle (LV), indicating a bifid cardiac apex

atrial septal defect ( J:315097 )

• at P0, 82% (23 of 28) of hearts show atrial septal defects

abnormal interventricular septum morphology ( J:315097 )

• formation of the interventricular septum is impaired: a deep fissure between the RV and LV is first seen at E11.5 and persists as a deep cleft separating the ventricles by E15.5

ventricular septal defect ( J:315097 )

• at P0, all hearts (28 of 28) exhibit ventricular septal defects

abnormal heart right ventricle morphology ( J:315097 )

• at E13.5, transcriptional regulation of RV development is severely disrupted

abnormal interventricular groove morphology ( J:315097 )

• at P0, all hearts (28 of 28) exhibit a deep interventricular groove

cellular

abnormal cell adhesion ( J:315097 )

• at E13.5, the RV of the heart shows decreased active (non-phosphorylated) beta-catenin staining between cell junctions

increased apoptosis ( J:315097 )

• at E11.5, cleaved caspase-3 staining shows significantly higher levels of apoptosis in the RV and the interventricular septum, but not in the LV, of the heart

• however, no differences in cell proliferation are detected in E11.5 heart sections

muscle

abnormal ventricle myocardium morphology ( J:315097 )

• at P0, the right ventricle (RV) myocardium shows an absence of long F-actin filaments

• at E13.5, active (non-phosphorylated) beta-catenin staining between cell junctions is decreased in the RV myocardium

• at E13.5, mRNA levels of several transcription factors involved in heart development (Gata4, Nkx2.5, Tbx5 and Hand2) are significantly decreased in the RV myocardium

• however, Tbx20 mRNA levels are normal in the RV at E13.5

trabecula carnea hypoplasia ( J:315097 )

• at P0, the right ventricle (RV) myocardium shows poor trabeculation

thin right ventricle myocardium compact layer ( J:315097 )

• at P0, the RV compact myocardium is significantly thinner than in control hearts

Genotype
MGI:7545224

cn8

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1Djk; Tg(Nkx2-5-cre)9Eno/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:321017 )

• although mice are alive from E11.5 to E18.5, all neonates are found dead at P0

cardiovascular system

abnormal cardiac outflow tract development ( J:321017 )

• at E14.5-P0, hearts exhibit impaired alignment of the outflow tract (OFT) to the ventricles

abnormal heart morphology ( J:321017 )

• at E14.5-P0, all (17 of 17) hearts display more than one type of congenital heart defect (CHD), not observed in control hearts

abnormal myocardium compact layer morphology ( J:321017 )

• at E15.5, the compact myocardium of both ventricles is poorly formed

thin myocardium compact layer ( J:321017 )

• at E14.5-P0, all hearts (17 of 17) exhibit a thin compact myocardium

thin ventricle myocardium compact layer ( J:321017 )

• at E15.5, both the left ventricle (LV) and right ventricle (RV) show a significant decrease in compact myocardium thickness relative to controls

abnormal ventricle myocardium morphology ( J:321017 )

• at E18.5, the ventricular myocardium shows severe disruption of F-actin filament organization

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

• however, no aberrant apoptosis is detected in the ventricular myocardium at E9.5

abnormal trabecula carnea morphology ( J:321017 )

• at E15.5, both the left ventricle (LV) and right ventricle (RV) show hypertrabeculation; the trabecular to compact myocardium ratio is increased by >2.5-fold relative to controls

abnormal heart development ( J:321017 )

• at E12.5, mRNA expression of Scrib and other cardiac transcription and growth factors (Nkx2.5, Gata4, Tbx5, Tbx20, Hand1, Hand2 and Bmp10) is significantly decreased relative to control hearts

abnormal fetal cardiomyocyte morphology ( J:321017 )

• at E18.5, cardiomyocytes in the ventricular myocardium exhibit a rounded morphology and appear highly disorganized in both the RV and LV while the short axis of cardiomyocyte diameter is significantly larger than in controls, indicating impaired cardiomyocyte polarization and elongation

• at E15.5, overall expression of SCRIB (scribble planar cell polarity protein) is significantly reduced in the myocardium surrounding the aorta (OFT), RV and LV, supporting a failure of cardiomyocytes to undergo polarization

double outlet right ventricle ( J:321017 )

• at E14.5-P0, 64.7% (11 of 17) hearts exhibit DORV: both pulmonary artery and aorta are connected to the right ventricle

overriding aortic valve ( J:321017 )

• at E14.5-P0, 35.3% (6 of 17) hearts exhibit and overriding aorta

abnormal heart apex morphology ( J:321017 )

• at E14.5-P0, all (17 of 17) hearts show a bifid cardiac apex (a bifurcation between the right and the left ventricle)

ventricular septal defect ( J:321017 )

• at E14.5-P0, all hearts (17 of 17) show ventricular septal defects

decreased fetal cardiomyocyte proliferation ( J:321017 )

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

cellular

decreased fetal cardiomyocyte proliferation ( J:321017 )

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

muscle

abnormal myocardium compact layer morphology ( J:321017 )

• at E15.5, the compact myocardium of both ventricles is poorly formed

thin myocardium compact layer ( J:321017 )

• at E14.5-P0, all hearts (17 of 17) exhibit a thin compact myocardium

thin ventricle myocardium compact layer ( J:321017 )

• at E15.5, both the left ventricle (LV) and right ventricle (RV) show a significant decrease in compact myocardium thickness relative to controls

abnormal ventricle myocardium morphology ( J:321017 )

• at E18.5, the ventricular myocardium shows severe disruption of F-actin filament organization

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

• however, no aberrant apoptosis is detected in the ventricular myocardium at E9.5

abnormal trabecula carnea morphology ( J:321017 )

• at E15.5, both the left ventricle (LV) and right ventricle (RV) show hypertrabeculation; the trabecular to compact myocardium ratio is increased by >2.5-fold relative to controls

decreased fetal cardiomyocyte proliferation ( J:321017 )

• at E9.5, the cell proliferation rate in the ventricular myocardium is significantly lower than in control hearts, as assessed by the percentage of pHH3+ and cyclin D1+ cardiomyocytes

Genotype
MGI:6107686

cn9

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1Djk; Tg(Pf4-icre)Q3Rsko/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

hematopoietic system

abnormal platelet activation ( J:214607 )

• phosphatidylserine (PS) exposure and microvesiculation nearly abolished after stimulation with thrombin or collagen in vitro

decreased platelet aggregation ( J:214607 )

• under shear in vitro

• reduced fibrin accumulation after laser-induced injury

• reduced thrombus formation after laser-induced injury

homeostasis/metabolism

abnormal platelet activation ( J:214607 )

• phosphatidylserine (PS) exposure and microvesiculation nearly abolished after stimulation with thrombin or collagen in vitro

decreased platelet aggregation ( J:214607 )

• under shear in vitro

• reduced fibrin accumulation after laser-induced injury

• reduced thrombus formation after laser-induced injury

Genotype
MGI:3654330

cn10

• 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

Genotype
MGI:3607402

cn11

• Allelic Composition: Rac1^tm1Djk/Rac1^tm1Djk; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1

endocrine/exocrine glands

abnormal sebocyte number ( J:99995 )

• an early increase in the number of terminally differentiated sebocytes is followed by progressive sebocyte loss

enlarged sebaceous gland ( J:99995 )

• 7 to 9 days after tamoxifen treatment sebaceous glands are enlarged and disorganized

integument

abnormal sebocyte number ( J:99995 )

• an early increase in the number of terminally differentiated sebocytes is followed by progressive sebocyte loss

enlarged sebaceous gland ( J:99995 )

• 7 to 9 days after tamoxifen treatment sebaceous glands are enlarged and disorganized

abnormal hair follicle morphology ( J:99995 )

• 11 to 15 days after tamoxifen treatment the hair follicle is reduced in size

absent hair follicle bulb ( J:99995 )

• the hair bulb is reduced and then absent following tamoxifen treatment

abnormal hair follicle infundibulum morphology ( J:99995 )

• 11 to 15 days after tamoxifen treatment the infundibulum degenerates into cysts

abnormal hair follicle bulge morphology ( J:99995 )

• depletion of stem cells is detected by the decreased expression of 3 hair follicle bulge markers

abnormal hair cycle ( J:99995 )

• pronounced defects in hair cycle are seen

abnormal epidermal layer morphology ( J:99995 )

• 3 to 5 days after tamoxifen treatment the interfollicular epidermis is thickened with an increase in cell numbers in the living and cornified layers and the infundibulum at the junction of the interfollicular epidermis and hair follicle is expanded

• 3 to 5 days after tamoxifen treatment the size of hemidesmosomes is reduced and later the numbers are reduced and those remaining are rudimentary

• 11 to 15 days after tamoxifen treatment partial to complete loss of viable interfollicular epidermal cell layers is seen

abnormal epidermis stratum basale morphology ( J:99995 )

• 7 to 9 days after tamoxifen treatment the basal layer is disorganized and has fewer, larger cells

abnormal skin cell number ( J:99995 )

• 3 to 5 days after tamoxifen treatment increased proliferation is seen in the epidermis, however from day 7 on proliferation is reduced

abnormal keratinocyte physiology ( J:99995 )

• in culture, treatment of keratinocytes with tamoxifen blocks clonal growth