Phenotypes Associated with This Genotype

Genotype
MGI:5503192

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Twist2^{tm1.1(cre)Dor}/Twist2⁺
• Genetic Background: B6.129-Twist2^{tm1.1(cre)Dor} Pten^tm1Hwu

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

Increase in mesenchymal cell proliferation in Pten^tm1Hwu/Pten^tm1Hwu Twist2^{tm1.1(cre)Dor}/Twist2⁺ mice

mortality/aging

neonatal lethality, complete penetrance ( J:192736 )

• mutants with less severe phenotypes die within 2-3 hours of birth, displaying cyanosis, chest retractions, and dyspnea

lethality throughout fetal growth and development, incomplete penetrance ( J:192736 )

• lethality between E15.5 and E18.5

respiratory system

abnormal lung morphology ( J:192736 )

• increase in collagen deposition in the lungs

• alveolar spaces are frequently lined by cuboidal cells with immature lamellar bodies

abnormal lung vasculature morphology ( J:192736 )

• reduction in distal capillary network density in E15.5 lungs

• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5

• increase in the distance between the capillaries and the lumen of the airways

abnormal lung development ( J:192736 )

• marker analysis indicates expansion of the distal epithelial progenitor cell domain

abnormal lung-associated mesenchyme development ( J:192736 )

• E18.5 lungs exhibit a hypercellular mesenchymal compartment

• more than 5-fold increase in the number of CD45-CD31+ embryonic mesenchymal progenitor side population (E-SP) and CD45-CD31- E-SP cell populations in E17.5 lungs indicating an increase in lung mesenchymal progenitor cell populations

respiratory distress ( J:192736 )

• in mutants with less severe phenotypes that die within hours of birth

cardiovascular system

abnormal lung vasculature morphology ( J:192736 )

• reduction in distal capillary network density in E15.5 lungs

• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5

• increase in the distance between the capillaries and the lumen of the airways

abnormal vascular development ( J:192736 )

• 44% of embryos lack of vascularization in entire embryos at E15.5

• E15.5 embryos show lack of vascularization in organs such as limbs and liver

• impaired differentiation of angioblasts into mature endothelial cells and blood vessels

hemorrhage ( J:192736 )

• 15% of embryos exhibit hemorrhage at E18.5

homeostasis/metabolism

decreased blood oxygen capacity ( J:192736 )

• newborns show a decrease in blood oxygenation

cyanosis ( J:192736 )

• in mutants with less severe phenotypes that die within hours of birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
persistent fetal circulation syndrome		DOID:13042	OMIM:265380	J:192736