Mouse Genome Informatics
hm
    Tlx3tm1Sjk/Tlx3tm1Sjk
involves: 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 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
• most newborn pups exhibit severe cyanosis

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

nervous system
N
• homozygotes show no major histopathologic abnormalities in cranial sensory neurons and brain nuclei (J:60751)
• no significant neuron loss or gliosis is observed (J:60751)
• 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
• 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
• 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
• newborn homozygotes always lack gastric milk

immune system
N
• newborn homozygotes display fully developed spleens (J:60751)

digestive/alimentary system
N
• newborn homozygotes do not display colonic abnormalities (J:60751)

Mouse Models of Human Disease
OMIM IDRef(s)
Central Hypoventilation Syndrome, Congenital; CCHS 209880 J:60751