Phenotypes Associated with This Genotype

Genotype
MGI:2669096

• Allelic Composition: Tlx3^tm1Sjk/Tlx3^tm1Sjk
• Genetic Background: involves: 129X1/SvJ

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

mortality/aging

neonatal lethality, complete penetrance ( J:60751 )

• homozygotes develop to term but die shortly after birth from a central respiratory failure

• homozygotes die from hypoventilation within 24 hrs of birth, even when respiration is transiently initiated by mechanical stimulation

homeostasis/metabolism

cyanosis ( J:60751 )

• most newborn pups exhibit severe cyanosis

respiratory system

abnormal breathing pattern ( J:60751 )

• C4 vetral root recordings in medulla-spinal cord preparations from newborn homozygotes reveal a rapid respiratory rate with shorter inspiratory duration and intermittent respiratory arrest of ~7.4 sec in duration relative to wild-type controls

tachypnea ( J:60751 )

• during non-apnea periods, homozygotes display an increased respiratory rate relative to wild-type mice

apnea ( J:60751 )

• most newborn homozygotes display immediate apnea

• electromyographic activity of intercostal muscles indicates a high incidence of apnea episodes of up to 20 sec in duration

• mutant pups exhibit an average of ~13 apnea episodes of more than or equal to 5 sec during 10 min of observation relative to only 1 episode in wild-type mice

• the average duration of an apnea episode is nearly doubled in mutant mice relative to wild-type mice

respiratory distress ( J:60751 )

respiratory failure ( J:60751 )

nervous system

nervous system phenotype ( J:60751 )

N • homozygotes show no major histopathologic abnormalities in cranial sensory neurons and brain nuclei

N • no significant neuron loss or gliosis is observed

abnormal dorsal interneuron 2 morphology ( J:76655 )

• homozygotes display abnormal D2 interneuron development, as suggested by loss of Isl1 expression (a marker for D2 interneurons) in the dorsal spinal cord at E11.5

abnormal dorsal interneuron 4 morphology ( J:76655 )

• homozygotes display abnormal D4 interneuron development in the caudal spinal cord, as indicated by expression loss of both Lmx1b and Phox2a in ventrally migrating D4 interneurons at E11.5; in contrast, the most dorsal Lmx1b expression is unaffected

abnormal nervous system physiology ( J:60751 )

• newborn homozygotes display a functional disorder in the central pattern generator of respiration in the ventral medulla

• a coordinate pattern is observed in which failure of inspiratory neuron firing correlates with the respiratory arrest measured as C4 ventral root activity

behavior/neurological

absent gastric milk in neonates ( J:60751 )

• newborn homozygotes always lack gastric milk

immune system

immune system phenotype ( J:60751 )

N • newborn homozygotes display fully developed spleens

digestive/alimentary system

digestive/alimentary phenotype ( J:60751 )

N • newborn homozygotes do not display colonic abnormalities

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital central hypoventilation syndrome		DOID:0060731	OMIM:209880	J:60751