Phenotypes Associated with This Genotype

Genotype
MGI:4950663

• Allelic Composition: Adra2b^tm1Gsb/Adra2b^tm1Gsb
• Genetic Background: B6.129-Adra2b^tm1Gsb

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

Dilated right ventricle in Adra2b^tm1Gsb/Adra2b^tm1Gsb mice

mortality/aging

neonatal lethality, incomplete penetrance ( J:166788 )

• most homozygotes die during the day of birth; however, normal Mendelian ratios are obtained between E10.5 and E18.5

• treatment of pregnant mice with cyclopamine (a smoothened antagonist) from E17.5 significantly increases the % of homozygotes surviving the immediate neonatal period

growth/size/body

decreased birth weight ( J:166788 )

• at P0, body weight is significantly lower than that in wild-type controls

slow postnatal weight gain ( J:166788 )

• newborn homozygotes gain weight more slowly than wild-type controls

• however, drinking behavior is normal, as shown by the presence of gastric milk

homeostasis/metabolism

cyanosis ( J:166788 )

• homozygotes become cyanotic within hours of birth

respiratory system

abnormal lung development ( J:166788 )

• homozygotes show an early postnatal defect in lung maturation due to enhanced sonic hedgehog (SHH) signaling

• however, pulmonary vascular development is not significantly altered as shown by normal capillary density

increased mesenchymal cell proliferation involved in lung development ( J:166788 )

• enhanced sonic hedgehog (SHH) signaling results in increased mesenchymal proliferation

• at P0, mutant lungs show a significant increase in the rate of mitosis and expression of cell cycle regulators cyclin D1 and Ki67 relative to wild-type lungs

• inhibition of enhanced SHH signaling by the smoothened antagonist cyclopamine rescues the lung morphology and altered gene expression in P1 mutant mice

decreased lung weight ( J:166788 )

• at P0, lung weight is significantly lower than that in wild-type controls

abnormal pulmonary alveolus morphology ( J:166788 )

• several hours after birth, homozygotes display reduced alveolar spaces relative to wild-type controls

atelectasis ( J:166788 )

• early after birth, mutant lungs are less inflated than wild-type lungs

thick pulmonary interalveolar septum ( J:166788 )

• several hours after birth, homozygotes display thickened interalveolar septae relative to wild-type controls

respiratory failure ( J:166788 )

• homozygotes exhibit early postnatal respiratory failure

• however, a normal spontaneous breathing rate is observed immediately after birth

cardiovascular system

dilated heart right ventricle ( J:166788 )

• at P0, the right ventricle is significantly dilated relative to that in wild-type hearts

• however, cardiac structure and function is normal with no significant differences in cardiac rhythm, ECG recordings or closure of the ductus arteriosus relative to wild-type controls

hematopoietic system

hematopoietic system phenotype ( J:166788 )

N • at P0, homozygotes display normal erythrocyte counts and morphology as well as normal hemoglobin synthesis relative to wild-type controls

cellular

increased mesenchymal cell proliferation involved in lung development ( J:166788 )

• enhanced sonic hedgehog (SHH) signaling results in increased mesenchymal proliferation

• at P0, mutant lungs show a significant increase in the rate of mitosis and expression of cell cycle regulators cyclin D1 and Ki67 relative to wild-type lungs

• inhibition of enhanced SHH signaling by the smoothened antagonist cyclopamine rescues the lung morphology and altered gene expression in P1 mutant mice