Phenotypes Associated with This Genotype

Genotype
MGI:4939046

• Allelic Composition: Tmem38b^tm1Hta/Tmem38b^tm1Hta
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

mortality/aging

neonatal lethality, complete penetrance ( J:150355 )

• homozygotes die within an hour of birth

respiratory system

pulmonary vascular congestion ( J:150355 )

• newborn homozygotes display pulmonary congestion

abnormal lung development ( J:150355 )

• homozygotes display abnormal Ca2+ handling and closely associated morphological and biochemical defects in alveolar type II cells during perinatal lung maturation

impaired lung alveolus development ( J:150355 )

• newborn homozygotes fail to form organized alveoli

abnormal lung saccule morphology ( J:150355 )

• at E18.5, mutant lungs display immature type II cells with poorly formed saccules or no saccules

abnormal pulmonary alveolus epithelial cell morphology ( J:150355 )

• newborn homozygotes show a >2-fold increase in the % of glycogen-rich cells in the alveolar epithelium relative to wild-type controls

• however, a normal population of type I and type II marker-positive cells are detected in mutant alveoli

abnormal type II pneumocyte morphology ( J:150355 )

• newborn homozygotes display immature type II cells with sparse microvilli, large glycogen deposits and insufficient lamellar bodies

abnormal alveolar lamellar body morphology ( J:150355 )

• lamellar body formation is severely impaired in mutant type II cells

• both the number and size of lamellar bodies are significantly reduced

decreased alveolar lamellar body number ( J:150355 )

• newborn homozygotes display significantly fewer lamellar body-positive cells than wild-type controls

small alveolar lamellar bodies ( J:150355 )

atelectasis ( J:150355 )

• newborn homozygotes fail to inflate their lungs

thick pulmonary interalveolar septum ( J:150355 )

• neonatal intra-alveolar septa remain thick

abnormal respiratory system physiology ( J:150355 )

• in culture, mutant alveolar type II cells show significantly lower resting cytoplasmic Ca2+ levels than wild-type cells in a normal bathing solution; however, similar resting levels are observed under Ca2+ free conditions

• neonatal mutant alveolar type II cells exhibit impaired IP3 receptor mediated Ca2+ release, despite Ca2+ overloading in intracellular stores

respiratory distress ( J:150355 )

• newborn homozygotes wriggle their bodies and gasp for breath

respiratory failure ( J:150355 )

• newborn homozygotes die of respiratory failure

abnormal surfactant composition ( J:150355 )

• both the major 16:0-16:1 and 16:0-16:0 phosphatidylcholine (PC) species and the minor PC species are significantly reduced in interstitial fractions from neonatal mutant lungs

• major phosphatidylglycerol (PG) species, including 16:0-16:1 and 16:0-16:0 PG, are reduced

• phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol species are also decreased

• no typical tubular myelin structures are observed, unlike in wild-type neonatal lungs

abnormal surfactant secretion ( J:150355 )

• secretion of surfactant phospholipids is impaired in neonatal mutant type II cells

homeostasis/metabolism

cyanosis ( J:150355 )

• newborn homozygotes appear cyanotic

hypoxia ( J:150355 )

• newborn homozygotes exhibit significantly reduced plasma O2 pressure and increased CO2 pressure, indicating severe hypoxia

abnormal calcium ion homeostasis ( J:150355 )

• newborn homozygotes display impaired Ca2+ handling in alveolar type II cells

acidosis ( J:150355 )

• newborn homozygotes display significantly reduced pH

cardiovascular system

pulmonary vascular congestion ( J:150355 )

• newborn homozygotes display pulmonary congestion