renal/urinary system phenotype

• single kidney
  • at P15, about 4% of heterozygotes exhibit unilateral renal agenesis
  (MGI Ref ID J:117753)

• decreased renal glomerulus number
  • at P15, heterozygotes show a reduced mean glomerular density relative to wild-type littermates (7.25 versus 8.95 glomeruli per unit area, respectively)
  (MGI Ref ID J:117753)

digestive/alimentary phenotype

• intestinal hypoperistalsis
  • decrease in both longitudinal and circular muscle contraction of the intestine in response to electric field stimulation
  (MGI Ref ID J:82456)

muscle phenotype

• intestinal hypoperistalsis
  • decrease in both longitudinal and circular muscle contraction of the intestine in response to electric field stimulation
  (MGI Ref ID J:82456)

nervous system phenotype

• abnormal enteric neuron morphology
  • colon submucosal neuron size is reduced by 16%, however cell size of small bowel submucosal neurons and myenteric and submucosal neuron numbers in the small bowel and colon are normal
  (MGI Ref ID J:82456)
  • the myenteric plexus has a 35% reduction in cell size in the small bowel and 34% reduction in the colon
  (MGI Ref ID J:82456)
  • myenteric neuron acetylcholinesterase-stained fiber counts are reduced by 11-13%
  (MGI Ref ID J:82456)

• abnormal neurotransmitter secretion
  • 70-95% reduction in substance P and VIP release
  (MGI Ref ID J:82456)

mortality/aging

• neonatal lethality, complete penetrance
  (MGI Ref ID J:30389)
  • death occurred 16-24 hours after birth
  (MGI Ref ID J:23852)

muscle phenotype

• intestinal hypoperistalsis
  (MGI Ref ID J:30389)
  • failure of milk to progress from the stomach to the intestine
  (MGI Ref ID J:23852)

nervous system phenotype

• abnormal cardiac ganglion morphology
  • cardiac ganglion volume was 56% smaller than controls, due to a reduction in neuronal cell number
  (MGI Ref ID J:64539)

• absent enteric neurons
  (MGI Ref ID J:30389)
  • neurons and glia were absent from the distal stomach, duodenum, small and large intestine, but not the esophagus or the proximal stomach as determined by TH, NF or MASH-1 immunoreactivity
  (MGI Ref ID J:30830)
  • no neurons in the small or large intestine, esophagus or stomach
  (MGI Ref ID J:23852)

• abnormal parasympathetic postganglionic fiber morphology
  • in two of six hearts, the AV node, the AV bundle and the proximal bundle branches were devoid of cholinergic fibers
  (MGI Ref ID J:64539)

• absent superior cervical ganglion
  • absent as early as E12.5, while all other sympathetic ganglia were present
  (MGI Ref ID J:30830)

• abnormal stellate ganglion morphology
  • occasionally larger than in controls
  (MGI Ref ID J:30830)

cellular phenotype

• increased metanephric mesenchyme apoptosis
  • the metanephric mesenchyme underwent apoptosis at E12.5
  (MGI Ref ID J:84282)

• abnormal enteric neural crest cell migration
  • mutant enteric crest cells were detected in the esophagus and proximal stomach, but not the rest of the gastrointestinal tract
  (MGI Ref ID J:30830)

renal/urinary system phenotype

• abnormal metanephric mesenchyme morphology
  • the metanephric mesenchyme did not condense by E11.5
  (MGI Ref ID J:84282)

• abnormal ureter development
  • reduced branching of the ureter
  (MGI Ref ID J:23852)

• dilated renal glomerular capsule
  (MGI Ref ID J:30389)

• small kidney
  • rudimetary and are of similar size to the adrenal glands when present
  (MGI Ref ID J:30389)

• abnormal kidney collecting duct morphology
  • absence of mature collecting ducts
  (MGI Ref ID J:23852)

• abnormal ureteric bud elongation
  • when the uteric bud was present, growth was retarded
  (MGI Ref ID J:84282)

• absent nephrogenic zone
  • no recognizable nephrogenic zone
  (MGI Ref ID J:23852)

• absent ureter
  • sometimes absent
  (MGI Ref ID J:30389)(MGI Ref ID J:23852)

• dilated renal tubules
  (MGI Ref ID J:30389)

• abnormal branching involved in ureteric bud morphogenesis
  • of those buds that entered the mesenchyme, the growth and branching was abnormal, if occuring at all
  (MGI Ref ID J:84282)

• abnormal kidney morphology
  • remaining kidney rudiments are dysplastic with few nephric elements (proximal and distal tubules, glomeruli, and vessels) and no recognizable medulla, cortex, or nephrogenic zone
  (MGI Ref ID J:23852)
  • dysplastic
  (MGI Ref ID J:30389)

• abnormal ureter morphology
  • variable severity; some animals exhibited an absent ureter and kidney, while others exhibited blind ureters with no renal tissue
  (MGI Ref ID J:23852)
  • sometimes absent or blind-ending
  (MGI Ref ID J:30389)

• abnormal ureteric bud invasion
  • when the uteric bud was present, growth was retarded and either failed to enter the mesenchyme or was delayed; at E11.0, 8% of the mutant buds had entered the mesenchyme
  (MGI Ref ID J:84282)
  • in approximately half of the mutant embryos, the uteric bud failed to evaginate although a mesenchymal blastema and a Wollfian duct were present in metanephroi
  (MGI Ref ID J:84282)

• blind ureter
  (MGI Ref ID J:23852)
  • sometimes blind-ending
  (MGI Ref ID J:30389)

• abnormal kidney mesenchyme morphology
  • persistence of large regions of undifferentiated mesenchyme
  (MGI Ref ID J:23852)

• absent kidney
  • variable penetrance
  (MGI Ref ID J:30389)
  • variable penetrance; kidneys are absent or rudimetary; both unilateral and bilateral effects were observed
  (MGI Ref ID J:23852)

• increased metanephric mesenchyme apoptosis
  • the metanephric mesenchyme underwent apoptosis at E12.5
  (MGI Ref ID J:84282)

digestive/alimentary phenotype

• intestinal hypoperistalsis
  • failure of milk to progress from the stomach to the intestine
  (MGI Ref ID J:23852)(MGI Ref ID J:30389)

respiratory system phenotype

• abnormal lung development
  • underdeveloped or collapsed lungs; likely a secondary effect of deficient amniotic fluid production by the kidneys
  (MGI Ref ID J:30389)

embryo phenotype

• abnormal enteric neural crest cell migration
  • mutant enteric crest cells were detected in the esophagus and proximal stomach, but not the rest of the gastrointestinal tract
  (MGI Ref ID J:30830)

• abnormal mesonephros morphology
  • reduced numbers of mesonephric tubules were observed at E11.5
  (MGI Ref ID J:84282)

• increased metanephric mesenchyme apoptosis
  • the metanephric mesenchyme underwent apoptosis at E12.5
  (MGI Ref ID J:84282)

homeostasis/metabolism phenotype

• oligohydramnios
  • deficient amniotic fluid production by the kidneys
  (MGI Ref ID J:30389)

mammalian phenotype

• cardiovascular system phenotype
  • Normal - no gross abnormalities, the ventricles, atria, valves, aorta and pulmonary trunk showed no defects
  (MGI Ref ID J:64539)

nervous system phenotype

• abnormal enteric ganglia morphology
  • display a nearly complete absence of the enteric ganglia throughout the entire gastrointestinal tract
  (MGI Ref ID J:135153)

• abnormal enteric nervous system morphology
  • absence of neurofilament labeling in latissimus dorsi muscle of P0 mice
  (MGI Ref ID J:135153)

renal/urinary system phenotype

• absent kidney
  (MGI Ref ID J:135153)

mammalian phenotype

• endocrine/exocrine gland phenotype
  • Normal - adrenal chromaffin cells develop normally, despite high levels of Ret expression occuring in normal development of these cells
  (MGI Ref ID J:82111)