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Phenotypes Associated with This Genotype
Genotype
MGI:2662356
Allelic
Composition
Slit3tm1Dor/Slit3tm1Dor
Genetic
Background
involves: 129S1/Sv * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slit3tm1Dor mutation (1 available); any Slit3 mutation (80 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Congenital diaphragmatic hernia (CDH) and lung pathology in Slit3tm1Dor/Slit3tm1Dor mice

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

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

liver/biliary system
• 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
• homozygotes display late-stage herniation of the transverse colon, leading to intestinal obstruction
• after P30, homozygotes display intestinal obstruction due to late-stage herniation of the transverse colon

respiratory system
• homozygotes with end-stage CDH exhibit pulmonary congestion
• homozygotes with end-stage CDH display lung hemorrhage
• 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
• homozygotes with end-stage CDH are short of breath

cardiovascular system
• homozygotes with end-stage CDH exhibit pulmonary congestion
• homozygotes with end-stage CDH display lung hemorrhage

skeleton
• 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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/12/2024
MGI 6.23
The Jackson Laboratory