Phenotypes associated with this allele

• Allele Symbol: Tlx2^tm1Sjk
• Allele Name: targeted mutation 1, Stanley J Korsmeyer
• Allele ID: MGI:2655186
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tlx2^tm1Sjk/Tlx2^tm1Sjk	involves: 129/Sv * C57BL/6	MGI:2655191

Genotype
MGI:2655191

hm1

• Allelic Composition: Tlx2^tm1Sjk/Tlx2^tm1Sjk
• Genetic Background: involves: 129/Sv * C57BL/6

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

mortality/aging

premature death ( J:40722 )

• 36% of homozygotes die between 3 and 6 weeks of age

growth/size/body

postnatal growth retardation ( J:40722 )

• homozygotes often display growth retardation after weaning

distended abdomen ( J:40722 )

• homozygotes often display distended abdomens after weaning

digestive/alimentary system

abnormal large intestine morphology ( J:40722 )

distended cecum ( J:40722 )

• upon autopsy, symptomatic homozygotes display distended ceca packed with chyme

megacolon ( J:40722 )

• on a hybrid 129/Sv x C57BL/6 background, 43% of homozygotes develop symptomatic megacolon after 3 weeks of age, with no significant differences in the time of onset and frequency between males and females; the remaining 57% are asymptomatic

• upon autopsy, the proximal colon is always massively distended and packed with chyme, whereas the distal colon appears constricted

• only occasional homozygotes develop symptoms of megacolon after 7 weeks of age

• progeny of asymptomatic homozygotes display a reduced incidence of megacolon (18%)

• Background Sensitivity: susceptibility to megacolon appears to be reduced following initial backrossing onto the 129/Sv background

abnormal small intestine morphology ( J:40722 )

distended ileum ( J:40722 )

• upon autopsy, many homozygotes display a distended distal ileum

nervous system

nervous system phenotype ( J:40722 )

N • at P14, homozygotes are viable and overtly normal with no detectable abnormalities in sympathoadrenal cells or in cranial, dorsal root, sympathetic or parasympathetic ganglia

abnormal enteric ganglia morphology ( J:40722 )

• symptomatic homozygotes display a 47% increase in the number of myenteric ganglia per field in the proximal colon along with a 86% increase in the distal colon

• similar changes in the number of myenteric ganglia are observed in the proximal and distal colon of asymptomatic homozygotes, indicating that myenteric ganglia hyperplasia occurs before megacolon development

• myenteric ganglia from proximal and distal colon are significantly hypertrophic in both symptomatic and asymptomatic homozygotes relative to wild-type controls

• in contrast, the number and size of ganglia in the distal ileum is normal

• no changes in the average thickness of colonic circular and longitudinal muscle are observed, indicating normal smooth muscle growth

abnormal enteric neuron morphology ( J:40722 )

• symptomatic homozygotes exhibit a 60% increase in the number of myenetric neurons/ganglion in the proximal colon along with a 66% increase in the number of neurons/ganglion in the distal colon; similar changes are observed in asymptomatic homozygotes

• in addition, homozygotes show a 41% increase in NADPH diaphorase-stained inhibitory myenteric neurons/ganglion in proximal colon along with a 130% increase in distal colon

• in contrast, homozygotes display a 22% decrease in the number of neurons/ganglion in the distal ileum (with no apparent changes in proximal ileum), and a 58% decrease in NADPH-stained inhibitory neurons/ganglion in the distal ileum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intestinal pseudo-obstruction		DOID:0080072		J:40722