Phenotypes associated with this allele

• Allele Symbol: P2rx2^tm1Ckn
• Allele Name: targeted mutation 1, Debra A Cockayne
• Allele ID: MGI:2687349
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	P2rx2^tm1Ckn/P2rx2^tm1Ckn	involves: 129P2/OlaHsd * C57BL/6	MGI:2687352
cx2	P2rx2^tm1Ckn/P2rx2^tm1Ckn P2rx3^tm1Ckn/P2rx3^tm1Ckn	involves: 129P2/OlaHsd * C57BL/6	MGI:2687353

Genotype
MGI:2687352

hm1

• Allelic Composition: P2rx2^tm1Ckn/P2rx2^tm1Ckn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

respiratory system

decreased pulmonary ventilation ( J:86890 )

• in response to hypoxia (10% O₂), adult homozygotes (4-6 months of age) display a significantly reduced ventilatory response showing an increase of only 261 +/- 202 ml/min/kg in minute ventilation (V_E) relative to 1008 +/- 154 ml/min/kg in wild-type controls

• in response to further hypoxia (7.5% O₂), homozygotes display a severe ventilatory depression with the V_E reduced below prehypoxic levels by 606 +/- 209 ml/min/kg, unlike wild-type controls where no additional increase in ventilation is observed but the V_E remains above normoxic levels

• however, adult homozygotes display normal resting ventilation during normoxia and show normal ventilatory responses to a mild (15% O₂) hypoxia relative to wild-type controls

cardiovascular system

abnormal carotid body physiology ( J:86890 )

• homozygotes show a dramatic reduction in afferent nerve responses of the carotid sinus nerve to a decrease in oxygen tension (PO₂)

• unlike in in vitro carotid body-sinus nerve preparations from wild-type mice where sinus nerve discharge increases from baseline to a peak of 130.82 +/- 10.79 spikes/sec during hypoxia, the afferent discharge in preparations from mutant mice only reaches a peak of 58.13 +/- 9.40 spikes/sec, indicating that carotid body function is impaired

• the average peak firing rate of single units induced by hypoxia is significantly lower in carotid body-sinus nerve preparations from mutant mice (1.64 +/- 0.11 spikes/sec) relative to that observed in wild-type preparations (7.96 +/- 0.88 spikes/sec)

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:86890 )

N • in response to hypoxia (7.5% O₂), adult homozygotes display normal decreases in body temperature relative to wild-type controls (0.9 +/- 0.2 vs 0.8 +/- 0.1 degress Celsius, respectively)

Genotype
MGI:2687353

cx2

• Allelic Composition: P2rx2^tm1Ckn/P2rx2^tm1Ckn; P2rx3^tm1Ckn/P2rx3^tm1Ckn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

decreased survivor rate ( J:86890 )

• only ~10% of double homozygotes survive through weaning, without displaying any gross pathological abnormalities in adulthood

postnatal lethality, incomplete penetrance ( J:86890 )

• >90% of double homozygotes die between birth and weaning showing pulmonary infection and bronchial pneumonia

respiratory system

respiratory system phenotype ( J:86890 )

N • surviving double homozygotes display normal ventilatory responses to varying levels of hypercapnia relative to wild-type controls: no significant differences in respiratory rate (f_R) and tidal volume (V_T) are noted at hypercapnic conditions when CO₂ levels increase to 3% and then to 6%

lung inflammation ( J:86890 )

• double homozygotes that die between birth and weaning exhibit bronchial pneumonia, as shown by postmortem examination

decreased pulmonary ventilation ( J:86890 )

• in response to hypoxia (10% O₂), adult double homozygotes (4-6 months of age) display a significantly reduced ventilatory response showing an increase of only 129 +/- 154 ml/min/kg in minute ventilation (V_E) relative to 979 +/- 161 ml/min/kg in wild-type controls

• in response to further hypoxia (7.5% O₂), double homozygotes display a severe ventilatory depression with the V_E reduced below prehypoxic levels by 555 +/- 137 ml/min/kg, unlike wild-type controls where no additional increase in ventilation is observed but the V_E remains above normoxic levels

• however, adult double homozygotes display normal resting ventilation during normoxia and show normal ventilatory responses to a mild (15% O2) hypoxia relative to wild-type controls

cardiovascular system

abnormal carotid body physiology ( J:86890 )

• unlike in in vitro carotid body-sinus nerve preparations from wild-type mice where sinus nerve discharge increases from baseline to a peak of 130.82 +/- 10.79 spikes/sec during hypoxia, the afferent discharge in preparations from double mutant mice only reaches a peak of 32.80 +/- 6.97 spikes/sec; this response is even smaller than that observed in preparations from single P2rx2^tm1Ckn mice (58.13 +/- 9.40 spikes/sec)

• the average peak firing rate of single units induced by hypoxia is significantly lower in carotid body-sinus nerve preparations from double mutant mice (1.19 +/- 0.10 spikes/sec) relative to that observed in preparations from wild-type (7.76 +/- 0.99 spikes/sec) and single P2rx2^tm1Ckn mutant mice (1.64 +/- 0.11 spikes/sec)

immune system

lung inflammation ( J:86890 )

• double homozygotes that die between birth and weaning exhibit bronchial pneumonia, as shown by postmortem examination

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:86890 )

N • in response to hypoxia (7.5% O₂), adult double homozygotes display normal decreases in body temperature relative to wild-type controls (1.1 +/- 0.2 vs 1.1 +/- 0.3 degrees Celsius, respectively)