Phenotypes associated with this allele

• Allele Symbol: Slit3^tm1Dor
• Allele Name: targeted mutation 1, David M Ornitz
• Allele ID: MGI:2662346
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slit3^tm1Dor/Slit3^tm1Dor	involves: 129S1/Sv * C57BL/6J	MGI:2662356

Genotype
MGI:2662356

hm1

• Allelic Composition: Slit3^tm1Dor/Slit3^tm1Dor
• Genetic Background: involves: 129S1/Sv * C57BL/6J

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

Congenital diaphragmatic hernia (CDH) and lung pathology in Slit3^tm1Dor/Slit3^tm1Dor mice

mortality/aging

premature death ( J:83292 )

• 24% of homozygotes die by 40 days of age

• 58% of homozygotes die by 150 days of age

• homozygotes appear to die from lung compression and intestinal obstruction

growth/size/body

decreased body weight ( J:83292 )

• after P30, homozygotes display a significantly reduced body weight relative to wild-type and heterozygous control mice

muscle

abnormal diaphragm development ( J:83292 )

• at E14.5, the mutant diaphragm mesenchyme is significantly thinner than normal

• at E18.5, the mesothelium of the hernia sac remains continuous with the pleural mesothelium of the diaphragm

abnormal diaphragm central tendon morphology ( J:83292 )

• at E13.5, the proliferation rate of mesenchymal cells in the central tendon is reduced by 22%, which may account for the reduced thickness of this region; however, no increased apoptosis is detected in the central tendon at E15.5

• at E15.5, the central tendon remains adherent to the liver with little mesenchymal tissue and no falciform ligament

diaphragmatic hernia ( J:83292 )

• >90% of homozygotes that die before 9 months of age display a central (septum transversum) congenital diaphragmatic hernia (CDH) in which the liver enters the thoracic cavity

• overall, 68% of homozygotes develop CDH, with a higher penetrance in males (74%) than females (60%)

• the central tendon region of the diaphragm fails to separate from liver tissue during embryonic development, such that at early postnatal stages up to P14, the liver is the only contents of the hernia sac and is always adherent to the hernia sac

• at later stages of herniation, other abdominal organs are noted in the sac including the intestine and gall bladder but never the stomach

• the size and degree of herniation is variable and progressive with age

thin diaphragm muscle ( J:83292 )

• homozygotes develop a central CDH by stretching of an abnormally thin diaphragm tissue which fails to separate from an expanding liver

liver/biliary system

absent falciform ligament ( J:83292 )

herniated liver ( J:83292 )

• 68% of homozygotes develop a central CDH with the liver extending into the thoracic cavity

• herniated liver tissue is often vacuolated and in the early stages of necrosis

digestive/alimentary system

herniated intestine ( J:83292 )

• homozygotes display late-stage herniation of the transverse colon, leading to intestinal obstruction

absent falciform ligament ( J:83292 )

intestinal obstruction ( J:83292 )

• after P30, homozygotes display intestinal obstruction due to late-stage herniation of the transverse colon

respiratory system

pulmonary vascular congestion ( J:83292 )

• homozygotes with end-stage CDH exhibit pulmonary congestion

lung hemorrhage ( J:83292 )

• homozygotes with end-stage CDH display lung hemorrhage

atelectasis ( J:83292 )

• homozygotes with end-stage CDH exhibit atelectasis due to pulmonary congestion

• however, no lung pathology is observed in mutant embryos or in newborn and young homozygotes in the early stages of herniation

• homozygotes that do not develop CDH (32%) exhibit normal lung morphology

respiratory distress ( J:83292 )

• homozygotes with end-stage CDH are short of breath

cardiovascular system

pulmonary vascular congestion ( J:83292 )

• homozygotes with end-stage CDH exhibit pulmonary congestion

lung hemorrhage ( J:83292 )

• homozygotes with end-stage CDH display lung hemorrhage

skeleton

absent falciform ligament ( J:83292 )

abnormal diaphragm central tendon morphology ( J:83292 )

• at E13.5, the proliferation rate of mesenchymal cells in the central tendon is reduced by 22%, which may account for the reduced thickness of this region; however, no increased apoptosis is detected in the central tendon at E15.5

• at E15.5, the central tendon remains adherent to the liver with little mesenchymal tissue and no falciform ligament

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital diaphragmatic hernia		DOID:3827	OMIM:142340 OMIM:222400 OMIM:610187	J:83292