Phenotypes associated with this allele

• Allele Symbol: P2rx4^tm1Ando
• Allele Name: targeted mutation 1, Joji Ando
• Allele ID: MGI:3612982
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	P2rx4^tm1Ando/P2rx4^tm1Ando	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:7628177
hm2	P2rx4^tm1Ando/P2rx4^tm1Ando	Not Specified	MGI:3613446
cx3	Entpd8^tm1Ktak/Entpd8^tm1Ktak P2rx4^tm1Ando/P2rx4^tm1Ando	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:7628176

Genotype
MGI:7628177

hm1

• Allelic Composition: P2rx4^tm1Ando/P2rx4^tm1Ando
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

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

hematopoietic system

abnormal neutrophil physiology ( J:311564 )

• stimulation with ATP-gammaS fails to stimulate basal and maximal values of extracellular acidification rates or oxygen consumption rates in colonic neutrophils

digestive/alimentary system

digestive/alimentary phenotype ( J:311564 )

N • numbers of neutrophils, dendritic cells, and macrophages in the large intestinal lamina propria are similar to wild-type controls under homeostatic conditions

N • under homeostatic conditions intestinal epithelial permeability is similar to controls

N • dextran sodium sulfate induced colitis is similar to wild-type controls

immune system

abnormal neutrophil physiology ( J:311564 )

• stimulation with ATP-gammaS fails to stimulate basal and maximal values of extracellular acidification rates or oxygen consumption rates in colonic neutrophils

Genotype
MGI:3613446

hm2

• Allelic Composition: P2rx4^tm1Ando/P2rx4^tm1Ando
• Genetic Background: Not Specified

cardiovascular system

abnormal common carotid artery morphology ( J:104459 )

• the diameter of the right common carotid artery is reduced and its walls are thicker

increased mean systemic arterial blood pressure ( J:104459 )

• homozygotes display a higher mean arterial pressure than wild-type controls

• however, no significant difference in heart rate is observed

abnormal blood vessel physiology ( J:104459 )

• unlike in wild-type controls, chronic ligation of the left external carotid artery fails to result in a reduction in the lumen diameter of the left common carotid artery and medial wall thickness is increased, indicating a defect in flow-dependent vascular remodeling

abnormal vascular endothelial cell physiology ( J:104459 )

• in response to blood flow stimulation, isolated mutant endothelial cells fail to exhibit a shear stress-dependent increase in Ca²⁺ influx and subsequent production of the potent vasodilator nitric oxide (NO)

• adenovirus vector-mediated gene transfer rescues the impaired flow-induced influx of Ca²⁺ and production of NO in cultured endothelial cells

abnormal vasodilation ( J:104459 )

• ATP-, but not acetylcholine-induced, vasodilation is significantly suppressed in preconstricted mutant cremaster muscle arterioles relative to wild-type arterioles

• following occlusion of one arteriole branch with a glass micropipette to increase blood flow through the other branch, flow-induced vasodilation is significantly reduced in mutant cremaster muscle arterioles relative to wild-type arterioles

• both ATP- and flow-induced (shear stress, 20 dynes/cm²), but not acetylcholine-induced, vasodilation is significantly reduced in mutant mesenteric arteries relative to wild-type arteries

• addition of EGTA or L-NAME significantly reduces flow-induced vasodilation in both genotypes, indicating that Ca²⁺ influx and NO mediate the vasodilatory response

muscle

abnormal vasodilation ( J:104459 )

• ATP-, but not acetylcholine-induced, vasodilation is significantly suppressed in preconstricted mutant cremaster muscle arterioles relative to wild-type arterioles

• following occlusion of one arteriole branch with a glass micropipette to increase blood flow through the other branch, flow-induced vasodilation is significantly reduced in mutant cremaster muscle arterioles relative to wild-type arterioles

• both ATP- and flow-induced (shear stress, 20 dynes/cm²), but not acetylcholine-induced, vasodilation is significantly reduced in mutant mesenteric arteries relative to wild-type arteries

• addition of EGTA or L-NAME significantly reduces flow-induced vasodilation in both genotypes, indicating that Ca²⁺ influx and NO mediate the vasodilatory response

homeostasis/metabolism

abnormal nitric oxide homeostasis ( J:104459 )

• mutant endothelial cells fail to exhibit flow-induced production of NO

• homozygotes excrete reduced amounts of NO products in urine

decreased urine nitrite level ( J:104459 )

• homozygotes show a significant reduction in the daily amount of nitrite (and nitrate) excreted in urine relative to wild-type controls

renal/urinary system

decreased urine nitrite level ( J:104459 )

• homozygotes show a significant reduction in the daily amount of nitrite (and nitrate) excreted in urine relative to wild-type controls

Genotype
MGI:7628176

cx3

• Allelic Composition: Entpd8^tm1Ktak/Entpd8^tm1Ktak; P2rx4^tm1Ando/P2rx4^tm1Ando
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

digestive/alimentary system

abnormal susceptibility to induced colitis ( J:311564 )

• severity of dextran sodium sulfate (DSS)-induced colitis is reduced compared to mutant mice wild-type for P2rx4

• reduction in the numbers of neutrophils and macrophages and partial reduction in the numbers of dendritic cells in mice with DSS-induced colitis compared to mutant mice wild-type for P2rx4

immune system

abnormal susceptibility to induced colitis ( J:311564 )

• severity of dextran sodium sulfate (DSS)-induced colitis is reduced compared to mutant mice wild-type for P2rx4

• reduction in the numbers of neutrophils and macrophages and partial reduction in the numbers of dendritic cells in mice with DSS-induced colitis compared to mutant mice wild-type for P2rx4