Phenotypes associated with this allele

• Allele Symbol: Phox2b^tm1Rth
• Allele Name: targeted mutation 1, David H Rowitch
• Allele ID: MGI:5575410
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Phox2b^tm1Rth/Phox2b^+ Hprt1^tm1(CAG-cre)Mnn/?	involves: 129 * 129S1/Sv * C57BL/6	MGI:7397263
cn2	Phox2b^tm1Rth/Phox2b^+ Tg(Fabp7-cre,-lacZ)3Gtm/0	involves: 129 * C57BL/6 * CBA	MGI:7397265

Genotype
MGI:7397263

cn1

• Allelic Composition: Phox2b^tm1Rth/Phox2b⁺; Hprt1^{tm1(CAG-cre)Mnn}/?
• Genetic Background: involves: 129 * 129S1/Sv * C57BL/6

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

mortality/aging

perinatal lethality, complete penetrance ( J:331513 )

• perinatal lethality, with death before P1

respiratory system

respiratory failure ( J:331513 )

• harvest just prior to birth at E18.5, shows that only 33% of mutants take one spontaneous breath and no mutants show further spontaneous respiratory effort, become cyanotic, and all die within minutes of delivery

nervous system

abnormal trigeminal V mesencephalic nucleus morphology ( J:331513 )

• loss of TH neurons in the mesencephalic trigeminal nucleus nuclei

abnormal locus ceruleus morphology ( J:331513 )

• the locus coeruleus is abnormal and fails to express tyrosine hydroxylase (TH), indicating absence of TH neurons; sparse and small neuronal cell bodies are seen suggesting cellular loss/attrition of these neurons

abnormal innervation ( J:331513 )

• abnormalities in noradrenergic circuits, including caudal hindbrain nuclei A1/C2 and the forebrain projections of locus coeruleus to hypothalamus

abnormal neuron morphology ( J:331513 )

• loss of TH neurons in the locus coereleus, the dorsal motor nucleus of the vagus, and mesencephalic trigeminal nucleus nuclei

• however, neuronal precursors of the dorsal motor nucleus of the vagus (DMNV) are detectable at E13.5 indicating that progenitor specification occurs

• however, serotonergic neurons that express tryptophan hydroxylase and 5HT appear normal and no gross abnormalities in forebrain are seen

abnormal facial nerve morphology ( J:331513 )

• abnormal formation of the seventh cranial nerve (CNVII, facial nucleus) in the embryonic brainstem is due to failure of precursor migration

abnormal vagus nerve morphology ( J:331513 )

• loss of TH neurons in the dorsal motor nucleus of the vagus

abnormal nervous system electrophysiology ( J:331513 )

• electrophysiological recordings from E18.5 ex vivo brain stem shows depression of endogenous respiratory motor root output under baseline conditions and in response to the excitatory neuropeptide, substance P

homeostasis/metabolism

cyanosis ( J:331513 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital central hypoventilation syndrome		DOID:0060731	OMIM:209880	J:331513

Genotype
MGI:7397265

cn2

• Allelic Composition: Phox2b^tm1Rth/Phox2b⁺; Tg(Fabp7-cre,-lacZ)3Gtm/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

behavior/neurological

abnormal suckling behavior ( J:331513 )

• pups fail to nurse and gain adequate body weight

respiratory system

decreased pulmonary respiratory rate ( J:331513 )

• mice show spontaneous/continuous breathing, albeit at a slightly reduced frequency, and do not exhibit cyanosis

nervous system

nervous system phenotype ( J:331513 )

N • mice show normal locus coeruleus tyrosine hydroxylase + populations and normal number of serotonergic neurons expressing tryptophan hydroxylase

abnormal retrotrapezoid nucleus morphology ( J:331513 )

• brainstems show loss of the retrotrapezoid nucleus

abnormal facial nerve morphology ( J:331513 )

• brainstems show loss of the seventh cranial nerve (CNVII) nuclei

• abnormal formation of CNVII in the embryonic brainstem is due to failure of precursor migration