Phenotypes associated with this allele

• Allele Symbol: Arrb1^tm1Jse
• Allele Name: targeted mutation 1, J G Seidman
• Allele ID: MGI:2157962
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Arrb1^tm1Jse/Arrb1^tm1Jse	involves: 129X1/SvJ * Black Swiss	MGI:3628923
cx2	Arrb1^tm1Jse/Arrb1^tm1Jse Arrb2^tm1Rjl/Arrb2^tm1Rjl	involves: 129X1/SvJ * C57BL/6	MGI:4887408

Genotype
MGI:3628923

hm1

• Allelic Composition: Arrb1^tm1Jse/Arrb1^tm1Jse
• Genetic Background: involves: 129X1/SvJ * Black Swiss

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

cardiovascular system

abnormal cardiovascular system physiology ( J:44953 )

• adult male homozygotes exhibit increased sensitivity to beta-adrenergic stimulation, as shown by altered cardiac responses to isoproterenol

• notably, basal, isoproterenol-stimulated, and NaF-stimulated adenylyl cyclase activities remain normal in mutant heart membrane preparations

increased ventricle muscle contractility ( J:44953 )

• homozygotes show no significant differences in life expectancy, fertility, blood chemistry, mean resting blood pressure, resting heart rate, left ventricular ejection fraction or immune systems relative to wild-type mice

• however, in response to increasing concentrations of beta-agonist isoproterenol, homozygotes exhibit a significantly increased left ventricular ejection fraction (i.e. enhanced contractility) at each isoproterenol concentration relative to wild-type mice

increased heart rate ( J:44953 )

• homozygotes exhibit no differences in the isoproterenol-mediated increase in heart rate relative to wild-type mice except at the highest isoproterenol concentration used (0.2 mg/min/kg)

muscle

increased ventricle muscle contractility ( J:44953 )

• homozygotes show no significant differences in life expectancy, fertility, blood chemistry, mean resting blood pressure, resting heart rate, left ventricular ejection fraction or immune systems relative to wild-type mice

• however, in response to increasing concentrations of beta-agonist isoproterenol, homozygotes exhibit a significantly increased left ventricular ejection fraction (i.e. enhanced contractility) at each isoproterenol concentration relative to wild-type mice

Genotype
MGI:4887408

cx2

• Allelic Composition: Arrb1^tm1Jse/Arrb1^tm1Jse; Arrb2^tm1Rjl/Arrb2^tm1Rjl
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:159121 )

• double homozygotes die within 4 hrs of birth

respiratory system

abnormal lung development ( J:159121 )

• at E18.5, double mutant lungs display impaired prealveoli formation and a thick mesenchyme, indicating a delay in lung development

• mRNA microarray analysis revealed downregulation of a significant proportion of genes involved in various lung morphogenetic processes

decreased mesenchymal cell proliferation involved in lung development ( J:159121 )

• at E18.5, double mutant lungs exhibit a signicant decrease in cell proliferation in the mesenchymal compartment

abnormal lung saccule morphology ( J:159121 )

• at E18.5, peripheral saccules are undilated and lined by a cuboidal epithelium, suggesting pulmonary immaturity

thick lung-associated mesenchyme ( J:159121 )

• at E18.5, double mutant lungs display ia thick mesenchyme

abnormal type I pneumocyte morphology ( J:159121 )

• at E18.5, alveolar type I epithelial cells are missing, as indicated by absence of either AQP-5 or T1a staining in double mutant lungs

abnormal type II pneumocyte morphology ( J:159121 )

• at E18.5, double mutant type II pneumocytes show an abundant amount of cytoplasmic glycogen and lack the typical lamellar bodies normally found in the cytoplasm or in the lumen of peripheral airspaces

• at E18.5, type II cell differentiation is impaired, as indicated by absence of surfactant-associated protein C (SP-C) staining in alveolar epithelial cells

abnormal alveolar lamellar body morphology ( J:159121 )

• disorganized lamellar bodies at E18.5

small lung ( J:159121 )

• at E18.5, double mutant lungs are significantly smaller in size

decreased lung weight ( J:159121 )

• at E18.5, the average ratio of lung weight to wet body weight of double mutants is ~80% of that of wild-type controls

pulmonary hypoplasia ( J:159121 )

• at E18.5, double mutant lungs exhibit a signicant decrease in cell proliferation, in both epithelial and mesenchymal compartments

• however, no significant changes in the extent of apoptosis are observed

atelectasis ( J:159121 )

respiratory distress ( J:159121 )

• double homozygotes exhibit neonatal respiratory distress

decreased surfactant secretion ( J:159121 )

• at E18.5, SP-A and SP-C peptide levels as well as pro-SP-C protein levels are severely reduced

growth/size/body

decreased birth body size ( J:159121 )

• at birth, double homozygous mutant pups are generally smaller than control pups

decreased birth weight ( J:159121 )

• at birth, the average wet body weight of double homozygous mutant pups is ~60% of that of wild-type pups

decreased fetal weight ( J:159121 )

• at E18.5, the average wet body weight of double homozygous mutant fetuses is only ~60% of that of wild-type fetuses

behavior/neurological

no spontaneous movement ( J:159121 )

• at birth, double homozygous mutant pups lack spontaneous movement

homeostasis/metabolism

cyanosis ( J:159121 )

• at birth, double homozygous mutant pups appear cyanotic

cellular

decreased mesenchymal cell proliferation involved in lung development ( J:159121 )

• at E18.5, double mutant lungs exhibit a signicant decrease in cell proliferation in the mesenchymal compartment