Phenotypes associated with this allele

• Allele Symbol: Phox2b^tm2Jbr
• Allele Name: targeted mutation 2, Jean-Francois Brunet
• Allele ID: MGI:3773691
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Phox2b^tm2Jbr/Phox2b^+	involves: 129S2/SvPas	MGI:4418308
ht2	Phox2b^tm2Jbr/Phox2b^+	involves: 129S2/SvPas * C57BL/6	MGI:3797591
cx3	Kcnk5^Gt(KST024)Byg/Kcnk5^+ Phox2b^tm2Jbr/Phox2b^+	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:4437575

Genotype
MGI:4418308

ht1

• Allelic Composition: Phox2b^tm2Jbr/Phox2b⁺
• Genetic Background: involves: 129S2/SvPas

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

nervous system

abnormal neuron physiology ( J:155885 )

• the parafacial area e-pF oscillator exhibits only occasional motor activity bursts with reduced frequency compared to in wild-type mice

• rhythmic phrenic discharges are less frequent than in wild-type mice

• mice fail to exhibit an accelerated respiratory-like rhythm phrenic discharge in response to low pH challenge unlike similarly treated wild-type mice

• however, mice exhibit functional pre-Botzinger complex

Genotype
MGI:3797591

ht2

• Allelic Composition: Phox2b^tm2Jbr/Phox2b⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:131365 )

• die within the first hours after birth from respiratory failure

homeostasis/metabolism

cyanosis ( J:131365 )

respiratory system

abnormal respiration ( J:131365 )

abnormal lung volume ( J:131365 )

• mean respiratory minute volume (VE) during apnea-free periods of eupnoeic pups is depressed in mutants

abnormal breathing pattern ( J:131365 )

• mutants exhibit gasping behavior and breathing irregularity is significantly greater in mutants

• plethysmographic recordings immediately after delivery show a range of phenotypes; 3 of 18 mutants ventilate only by intermittent gasping, the remaining breathe rhythmically but at a slower rate or show chaotic breathing that is interrupted by periods of apnea

apnea ( J:131365 )

• apneic episodes are more frequent and last longer in mutants than in wild-type, resulting in a 6.5-fold higher total apnea duration

hypoventilation ( J:131365 )

• baseline ventilation in air is depressed in mutants

• mutants do not increase their ventilation in response to hypercapnia (elevated pCO2)

respiratory failure ( J:131365 )

• die within the first hours after birth from respiratory failure

nervous system

abnormal brain interneuron morphology ( J:131365 )

• loss of a set of parafacial interneurons in the RTN/pFRG region

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital central hypoventilation syndrome		DOID:0060731	OMIM:209880	J:131365

Genotype
MGI:4437575

cx3

• Allelic Composition: Kcnk5^{Gt(KST024)Byg}/Kcnk5⁺; Phox2b^tm2Jbr/Phox2b⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

nervous system

abnormal retrotrapezoid nucleus morphology ( J:157526 )

• retrotrapezoid nucleus neurons are absent