Phenotypes associated with this allele

• Allele Symbol: Cybb^tm1Din
• Allele Name: targeted mutation 1, Mary C Dinauer
• Allele ID: MGI:1857284
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cybb^tm1Din/Cybb^tm1Din	B6.129S-Cybb^tm1Din	MGI:3785289
hm2	Cybb^tm1Din/Cybb^tm1Din	B6.129S-Cybb^tm1Din/J	MGI:5486338
hm3	Cybb^tm1Din/Cybb^tm1Din	involves: 129S/SvEv * C57BL/6	MGI:3783586
cx4	Cybb^tm1Din/Cybb^tm1Din Nrros^tm1Lex/Nrros^tm1Lex	B6.129S-Nrros^tm1Lex Cybb^tm1Din	MGI:6144086
cx5	Cybb^tm1Din/Y Tg(SOD1*G93A)^dl1Gur/0	B6.Cg-Cybb^tm1Din Tg(SOD1*G93A)^dl1Gur	MGI:4440461
ot6	Cybb^tm1Din/Y	B6.129S-Cybb^tm1Din	MGI:4440459
ot7	Cybb^tm1Din/Y	involves: 129S/SvEv * C57BL/6	MGI:2449556
ot8	Cybb^tm1Din/?	B6.129S-Cybb^tm1Din/J	MGI:6802119

Genotype
MGI:3785289

hm1

• Allelic Composition: Cybb^tm1Din/Cybb^tm1Din
• Genetic Background: B6.129S-Cybb^tm1Din

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

immune system

immune system phenotype ( J:113463 )

♀N • mice exhibit a normal local Shwartman response namely thrombohemorrhagic vasculitis

increased acute inflammation ( J:110181 )

♀ • increased infiltration of leukocytes into gelatin sponge implanted along with QR-32 fibrosarcoma cells

granulomatous inflammation ( J:146231 )

♀ • zymosan injection into the peritoneal cavity results in an exaggerated influx of polymorphonuclear cells with declining numbers over the next 96 hours

♀ • macrophage numbers also become elevated and remain elevated for 96 hours

nervous system

reduced long-term potentiation ( J:111410 )

♀ • completely abrogated in hippocampal slices

decreased post-tetanic potentiation ( J:111410 )

♀ • significantly decreased

♀ • synaptic fatigue is normal

behavior/neurological

abnormal spatial learning ( J:111410 )

♀ • small but significant deficits in early training trials in water maze tests

♀ • spatial learning impairments

impaired coordination ( J:111410 )

♀ • very slightly impaired motor coordination in a rotarod test

decreased vertical activity ( J:111410 )

♀ • less rearing in open field tests

neoplasm

decreased metastatic potential ( J:110181 )

♀ • decreased metastasis of QR-32 fibrosarcoma cells implanted with a gelatin sponge to induce inflammation

♀ • greatly decreased metastasis of B16BL6 melanoma cells after implantation although cell growth was similar to that seen in controls

decreased tumor growth/size ( J:110181 )

♀ • reduced growth of QR-32 fibrosarcoma cells implanted with a gelatin sponge to induce inflammation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic granulomatous disease		DOID:3265	OMIM:PS306400	J:146231

Genotype
MGI:5486338

hm2

• Allelic Composition: Cybb^tm1Din/Cybb^tm1Din
• Genetic Background: B6.129S-Cybb^tm1Din/J

growth/size/body

decreased body weight ( J:235399 )

• mice appear normal at weaning but fail to gain weight

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:194294 )

♀N • wounded colonic epithelium exhibit normal phagocytic reactive oxygen species generation

increased circulating creatinine level ( J:235399 )

increased blood urea nitrogen level ( J:235399 )

abnormal circulating chemokine level ( J:235399 )

• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice

increased circulating interleukin-1 beta level ( J:235399 )

• in 52-week old mice

decreased circulating interleukin-10 level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-12b level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-6 level ( J:235399 )

• in 52-week old mice

increased urine protein level ( J:235399 )

hematopoietic system

increased neutrophil cell number ( J:235399 )

• increase in levels of circulating neutrophils

increased lymphocyte cell number ( J:235399 )

• increase in levels of circulating lymphocytes

increased monocyte cell number ( J:235399 )

• increase in levels of circulating monocytes

increased IgG level ( J:235399 )

• IgG deposition in the glomeruli of kidneys

abnormal macrophage physiology ( J:235399 )

• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages

• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity

immune system

increased neutrophil cell number ( J:235399 )

• increase in levels of circulating neutrophils

increased lymphocyte cell number ( J:235399 )

• increase in levels of circulating lymphocytes

increased monocyte cell number ( J:235399 )

• increase in levels of circulating monocytes

increased IgG level ( J:235399 )

• IgG deposition in the glomeruli of kidneys

abnormal macrophage physiology ( J:235399 )

• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages

• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity

abnormal circulating chemokine level ( J:235399 )

• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice

increased circulating interleukin-1 beta level ( J:235399 )

• in 52-week old mice

decreased circulating interleukin-10 level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-12b level ( J:235399 )

• in 52-week old mice

increased circulating interleukin-6 level ( J:235399 )

• in 52-week old mice

increased susceptibility to systemic lupus erythematosus ( J:235399 )

• mice develop a systemic lupus erythematosus-like disease (SLE)

increased autoantibody level ( J:235399 )

• increase in serum levels of a broad array of antibodies against autoantigens commonly associated with SLE

increased anti-nuclear antigen antibody level ( J:235399 )

increased anti-double stranded DNA antibody level ( J:235399 )

glomerulonephritis ( J:235399 )

• kidneys from aged mice show endocapillary proliferative glomerulonephritis

renal/urinary system

increased urine protein level ( J:235399 )

abnormal kidney morphology ( J:235399 )

• mice show indications of kidney damage and show increased functional markers of kidney injury

abnormal renal glomerulus morphology ( J:235399 )

• IgG and complement C1q deposition in the glomeruli of kidneys

glomerulonephritis ( J:235399 )

• kidneys from aged mice show endocapillary proliferative glomerulonephritis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:235399

Genotype
MGI:3783586

hm3

• Allelic Composition: Cybb^tm1Din/Cybb^tm1Din
• Genetic Background: involves: 129S/SvEv * C57BL/6

growth/size/body

decreased body weight ( J:115614 )

♀ • body weight is slightly but significantly reduced at 10-12 weeks of age

digestive/alimentary system

digestive/alimentary phenotype ( J:64232 )

♀N • susceptibility to indomethacin-induced changes in mucosa permeability is significantly attenuated relative to wild-type controls or Rag2-deficient mice

abnormal intestinal mucosa morphology ( J:64232 )

♀ • when given 10-20 mg/kg indomethacin, mice have markedly less damage to integrity of the small bowel mucosa than controls or Rag2-null mice which develop small nonhemorrhagic lesions in the jejunum

abnormal stomach mucosa morphology ( J:64232 )

♀ • when given 10-20 mg/kg indomethacin, mice have markedly less damage to integrity of the gastric mucosa than controls or Rag2-null mice which develop extensive hemorrhagic lesions of the gastric mucosa

immune system

immune system phenotype ( J:64232 )

♀N • mice develop minimal inflammation in response to indomethacin treatement compared to wild-type controls or Rag2-null animals

cardiovascular system

abnormal aorta tunica media morphology ( J:115614 )

♀ • medial area of the aorta is unaffected by angiotensin II infusion whereas it increases in controls

decreased systemic arterial blood pressure ( J:115614 )

♀ • baseline blood pressure is significantly reduced at 10-12 weeks of age

Genotype
MGI:6144086

cx4

• Allelic Composition: Cybb^tm1Din/Cybb^tm1Din; Nrros^tm1Lex/Nrros^tm1Lex
• Genetic Background: B6.129S-Nrros^tm1Lex Cybb^tm1Din

cellular

cellular phenotype ( J:209569 )

N • normal reactive oxygen species (ROS) production

immune system

immune system phenotype ( J:209569 )

N • normal susceptibility to, and bacterial burden in livers and spleens after, L. monocytogenes infection

Genotype
MGI:4440461

cx5

• Allelic Composition: Cybb^tm1Din/Y; Tg(SOD1*G93A)^dl1Gur/0
• Genetic Background: B6.Cg-Cybb^tm1Din Tg(SOD1*G93A)^dl1Gur

mortality/aging

premature death ( J:111782 )

♂ • life span improved relative to mice only carrying Tg(SOD1*G93A)^dl1Gur

behavior/neurological

abnormal righting response ( J:111782 )

♂ • used as a measure of paralysis

♂ • improved relative to mice only carrying Tg(SOD1*G93A)^dl1Gur

paralysis ( J:111782 )

♂ • reached end stage paralysis later than mice only carrying Tg(SOD1*G93A)^dl1Gur

nervous system

neurodegeneration ( J:111782 )

♂ • improved relative to mice only carrying Tg(SOD1*G93A)^dl1Gur

axon degeneration ( J:111782 )

♂ • 50% more anterior horn motor neurons in the anterior horn of the spinal cord than in mice only carrying Tg(SOD1*G93A)^dl1Gur

♂ • more myelinated axons in the 5th lumbar anterior roots than in mice only carrying Tg(SOD1*G93A)^dl1Gur

♂ • more innervated end plates than in mice only carrying Tg(SOD1*G93A)^dl1Gur

muscle

increased skeletal muscle fiber size ( J:111782 )

♂ • in the fibularis and peroneus longus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 1		DOID:0060193	OMIM:105400	J:111782

Genotype
MGI:4440459

ot6

• Allelic Composition: Cybb^tm1Din/Y
• Genetic Background: B6.129S-Cybb^tm1Din

growth/size/body

decreased body weight ( J:135786 )

♂

nervous system

abnormal long-term potentiation ( J:147954 )

♂ • chronic intermittent hypoxia fails to evoke sensory long-term facilitation in the carotid body

renal/urinary system

renal/urinary system phenotype ( J:101981 )

♂N • anesthetized males exhibit no significant differences in baseline glomerular filtration rate (GFR), urine flow, sodium excretion, and potassium excretion relative to wild-type controls

decreased renal plasma flow rate ( J:138704 )

♂ • proportionately greater decrease in renal blood flow after L-NAME administration than in controls

increased renal plasma flow rate ( J:101981 )

♂ • anesthetized males exhibit significantly higher baseline renal blood flow (RBF) relative to wild-type controls (4.3+/-0.4 versus 2.5+/-0.2 mL/min per gram, respectively)

♂ • in response to i.v. infusion of Ang II, anesthetized males show a smaller % of reduction in RBF relative to wild-type controls (-8% versus -33%, respectively)

decreased renal vascular resistance ( J:101981 , J:138704 )

♂ • anesthetized males exhibit significantly lower baseline renal vascular resistance (RVR) relative to wild-type controls (16+/-1.3 versus 29+/-2.3 mm Hg/mL/min per gram, respectively) (J:101981)

♂ • in response to i.v. infusion of Ang II, anesthetized males show a smaller % of increase in RVR relative to wild-type controls (+73% versus +173%, respectively) (J:101981)

♂ • after L-NAME administration relative to controls (J:138704)

increased urine creatinine level ( J:101981 )

♂ • conscious males exhibit a higher excretion rate of creatinine relative to wild-type controls (1.4+/-0.4 versus 1.0+/-0.2 mg/day per gram, respectively)

decreased urine sodium level ( J:138704 )

♂ • after L-NAME administration relative to controls

increased urine sodium level ( J:101981 )

♂ • conscious males exhibit a higher basal level of urinary sodium excretion relative to wild-type controls (807+/-69 versus 545+/-94 umol/day per gram, respectively)

♂ • however, the basal level of 24-hour urine flow is normal in conscious males

increased urine nitrite level ( J:101981 )

♂ • conscious males exhibit significantly higher urinary excretion of nitrate/nitrite relative to wild-type controls (23.7+/-3.0 versus 13.3+/-2.5 umol/day per gram, respectively)

increased renal glomerular filtration rate ( J:101981 )

♂ • in response to i.v. infusion of Ang II, anesthetized males show a 43% increase in GFR, unlike wild-type controls where GFR is not significantly altered

oliguria ( J:138704 )

♂ • reduced urine volume after L-NAME administration relative to controls

cardiovascular system

cardiovascular system phenotype ( J:101981 )

♂N • anesthetized males exhibit no significant differences in baseline mean arterial pressure relative to wild-type controls

♂N • conscious males show no significant differences in mean systolic arterial pressure relative to wild-type controls

♂N • i.v. administration of Ang II causes similar increments in mean arterial pressure in both genotypes

abnormal myocardial fiber morphology ( J:135786 )

♂

abnormal blood circulation ( J:138704 )

♂

decreased renal plasma flow rate ( J:138704 )

♂ • proportionately greater decrease in renal blood flow after L-NAME administration than in controls

increased renal plasma flow rate ( J:101981 )

♂ • anesthetized males exhibit significantly higher baseline renal blood flow (RBF) relative to wild-type controls (4.3+/-0.4 versus 2.5+/-0.2 mL/min per gram, respectively)

♂ • in response to i.v. infusion of Ang II, anesthetized males show a smaller % of reduction in RBF relative to wild-type controls (-8% versus -33%, respectively)

decreased renal vascular resistance ( J:101981 , J:138704 )

♂ • anesthetized males exhibit significantly lower baseline renal vascular resistance (RVR) relative to wild-type controls (16+/-1.3 versus 29+/-2.3 mm Hg/mL/min per gram, respectively) (J:101981)

♂ • in response to i.v. infusion of Ang II, anesthetized males show a smaller % of increase in RVR relative to wild-type controls (+73% versus +173%, respectively) (J:101981)

♂ • after L-NAME administration relative to controls (J:138704)

decreased right ventricle systolic pressure ( J:135786 )

♂ • right ventricular systolic pressure is not increased by intermittent hypoxic stress as it is in controls

homeostasis/metabolism

increased urine creatinine level ( J:101981 )

♂ • conscious males exhibit a higher excretion rate of creatinine relative to wild-type controls (1.4+/-0.4 versus 1.0+/-0.2 mg/day per gram, respectively)

abnormal nitric oxide homeostasis ( J:101981 )

♂ • conscious males exhibit a significantly higher 24-hour urinary excretion of NO metabolites, nitrate/nitrite, relative to wild-type controls, indicating an increase in NO bioavailability

♂ • however, no significant changes in urinary excretion of 8-isoprostane (an indirect marker for oxidative stress) are observed

decreased urine sodium level ( J:138704 )

♂ • after L-NAME administration relative to controls

increased urine sodium level ( J:101981 )

♂ • conscious males exhibit a higher basal level of urinary sodium excretion relative to wild-type controls (807+/-69 versus 545+/-94 umol/day per gram, respectively)

♂ • however, the basal level of 24-hour urine flow is normal in conscious males

increased urine nitrite level ( J:101981 )

♂ • conscious males exhibit significantly higher urinary excretion of nitrate/nitrite relative to wild-type controls (23.7+/-3.0 versus 13.3+/-2.5 umol/day per gram, respectively)

muscle

abnormal myocardial fiber morphology ( J:135786 )

♂

Genotype
MGI:2449556

ot7

• Allelic Composition: Cybb^tm1Din/Y
• Genetic Background: involves: 129S/SvEv * C57BL/6

growth/size/body

cardiac hypertrophy ( J:115652 )

♂ • Angiotensin II infusion causes a 5% cardiac mass change as compared to a 20% change in controls

decreased body weight ( J:115614 )

♂ • body weight is slightly but significantly reduced at 10-12 weeks of age

immune system

abnormal immune system physiology ( J:22868 )

♂

abnormal neutrophil physiology ( J:22868 )

♂ • neutrophils lacked respiratory burst activity

abnormal macrophage physiology ( J:22868 )

♂ • macrophages lacked respiratory burst activity

increased inflammatory response ( J:22868 )

♂ • dysregulated inflammatory response; increased numbers of peritoneal exudate neutrophils in chemical peritonitis induced by thioglycollate

increased susceptibility to infection ( J:22868 )

♂ • increased frequency of spontaneously occurring infections

increased susceptibility to bacterial infection ( J:22868 )

♂ • increased susceptibility to S. aureus infection and A. fumigatus infection

cardiovascular system

abnormal aorta tunica media morphology ( J:115614 )

♂ • medial area of the aorta is unaffected by angiotensin II infusion whereas it increases in controls

cardiac hypertrophy ( J:115652 )

♂ • Angiotensin II infusion causes a 5% cardiac mass change as compared to a 20% change in controls

decreased systemic arterial blood pressure ( J:115614 )

♂ • baseline blood pressure is significantly reduced at 10-12 weeks of age

decreased systemic arterial systolic blood pressure ( J:115652 )

♂ • lower baseline systolic pressure

hematopoietic system

abnormal neutrophil physiology ( J:22868 )

♂ • neutrophils lacked respiratory burst activity

abnormal macrophage physiology ( J:22868 )

♂ • macrophages lacked respiratory burst activity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chronic granulomatous disease		DOID:3265	OMIM:PS306400	J:22868

Genotype
MGI:6802119

ot8

• Allelic Composition: Cybb^tm1Din/?
• Genetic Background: B6.129S-Cybb^tm1Din/J

mortality/aging

postnatal lethality, incomplete penetrance ( J:306955 )

• during the first 3 weeks of life, mice exhibit a significantly lower survival rate than wild-type controls (72% vs 92%, respectively)

prenatal lethality, incomplete penetrance ( J:306955 )

• at birth (P0), litter size is reduced by about 25%, suggesting that embryos with severe growth retardation die during gestation

growth/size/body

embryonic growth retardation ( J:306955 )

decreased embryo size ( J:306955 )

• at E10.5-E12.5, six of 25 (24%) embryos show a significantly smaller body size than wild-type embryos

decreased birth weight ( J:306955 )

• at birth, body weight is significantly lower than in wild-type controls

embryo

embryonic growth retardation ( J:306955 )

decreased embryo size ( J:306955 )

• at E10.5-E12.5, six of 25 (24%) embryos show a significantly smaller body size than wild-type embryos

cardiovascular system

abnormal cardiac epithelial to mesenchymal transition ( J:306955 )

• at E10.5, full hearts show significantly reduced mRNA levels of Snai1 (a marker of epithelial to mesenchymal transition); at E12.5, the number of Snail1+ cells in the AV endocardial cushion are significantly lower than in wild-type hearts

• ex vivo, AV cushion explants of E10.5 hearts show a significantly lower number of spindle-shaped cells that have undergone endocardial-to-mesenchymal transition (EndMT) than wild-type cushions

• treatment of AV cushion explants with N-acetylcysteine (a ROS quenching agent) further reduces EndMT in AV cushions, as seen in wild-type samples

abnormal heart morphology ( J:306955 )

• 21 of 61 (34.4%) neonatal mice exhibit various congenital heart defects (CHDs)

abnormal heart development ( J:306955 )

• at E10.5, mRNA levels of genes critical to EndMT and AV endocardial cushion development (Gata4, Tgf2, Bmp2, Bmp4, and Snail1) are significantly lower than in wild-type hearts

abnormal atrioventricular cushion morphology ( J:306955 )

• at E10.5, AV endocardial cushions show a 2-fold increase in cell apoptosis, as quantified by cleaved caspase-3-positive cells

• at E12.5, AV cushions show a 50% lower cell proliferation rate, as determined by Ki67 immunostaining; cellular density is significantly lower than in wild-type AV endocardial cushions

abnormal atrioventricular valve morphology ( J:306955 )

• hearts with septal defects exhibit malformations of the atrioventricular (AV) valves

abnormal mitral valve morphology ( J:306955 )

• mitral valves are shortened in length and show a significant increase in total GAG+ (glycosaminoglycan-positive) area and in collagen deposition relative to wild-type valves

• the distal tip of mitral valves is enlarged

thick mitral valve cusps ( J:306955 )

abnormal tricuspid valve morphology ( J:306955 )

• tricuspid valves are shortened in length and show a significant increase in total GAG+ (glycosaminoglycan-positive) area and in collagen deposition relative to wild-type valves

• however, the distal tip of tricuspid valves is not enlarged

atrial septal defect ( J:306955 )

• 18% of mice are born with atrial septal defects (ASDs)

• most neonates exhibit a single ASD; however, 2 of 61 mice (3.3%) show both ASD and VSD

atrioventricular septal defect ( J:306955 )

• 3.3% of mice are born with atrioventricular canal defects (AVCDs)

ventricular septal defect ( J:306955 )

• 18% of mice are born with ventricular septal defects (VSDs)

• most neonates exhibit a single VSD; however, 2 of 61 mice (3.3%) show both ASD and VSD

bicuspid aortic valve ( J:306955 )

• 6.6% of neonates exhibit bicuspid aortic valve (BAV)

• all cases of BAV are associated with septal defects

cellular

increased apoptosis ( J:306955 )

• at E10.5, AV endocardial cushions show a 2-fold increase in cell apoptosis, as quantified by cleaved caspase-3-positive cells

decreased cell proliferation ( J:306955 )

• at E12.5, AV cushions show a 50% lower cell proliferation rate, as determined by Ki67 immunostaining

abnormal redox activity ( J:306955 )

• at E10.5, analysis of dihydroethidium fluorescence intensity showed significantly lower ROS levels in the myocardium than in wild-type controls

homeostasis/metabolism

abnormal glycosaminoglycan level ( J:306955 )

• both mitral and tricuspid valves show a significant increase in total GAG+ (glycosaminoglycan-positive) area relative to wild-type valves