Phenotypes Associated with This Genotype

Genotype
MGI:3812473

hm1

• Allelic Composition: Ada^tm1Mw/Ada^tm1Mw
• Genetic Background: involves: 129S7/SvEvBrd

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

growth/size/body

heart right ventricle hypertrophy ( J:231559 )

• mice develop right ventricle hypertrophy

• treatment with GS-6201 reduces right ventricle hypertrophy

cellular

increased vascular smooth muscle cell proliferation ( J:231559 )

• increase in proliferation of cells within the vascular wall of the lungs

maternal effect ( J:234143 )

• fetuses from pregnant mutant females are smaller and weigh less

cardiovascular system

abnormal lung vasculature morphology ( J:231559 )

• mice exhibit vascular remodeling in the lung

• increase in muscularization of vessels and a greater number of muscularized vessels are seen in the lung parenchyma

• treatment with GS-6201 inhibits the extent of muscularization but not the number of muscularized vessels

abnormal placenta vasculature ( J:234143 )

♀ • placentas show disorganized and impaired vasculature in the labyrinthine zone

♀ • treatment with adenosine deaminase enzyme therapy ameliorates placental defects

vascular smooth muscle hypertrophy ( J:231559 )

• thickening of the vascular smooth muscle wall in the lungs

• treatment with the ADORA2B antagonist GS-6201 reduces the thickening of the vascular smooth muscle wall

heart right ventricle hypertrophy ( J:231559 )

• mice develop right ventricle hypertrophy

• treatment with GS-6201 reduces right ventricle hypertrophy

increased right ventricle systolic pressure ( J:231559 )

• mice develop increased right ventricle systolic pressure

• treatment with GS-6201 reduces right ventricle systolic pressure

pulmonary hypertension ( J:231559 )

• mice exhibit hallmarks of pulmonary hypertension

• treatment with GS-6201 reduces the hallmarks of pulmonary hypertension

increased vascular smooth muscle cell proliferation ( J:231559 )

• increase in proliferation of cells within the vascular wall of the lungs

immune system

increased dendritic cell number ( J:138722 )

• the number of proangiogenic CD11b^lowCD11c+ dendritic cells in the lungs is increased by 3-fold and they exhibit increased size compared to in wild-type mice

abnormal dendritic cell physiology ( J:138722 )

• lung dendritic cells exhibit increased basal secretion levels of VEGF and CXCL1 and elevated VEGF production in response to NECA compared to in wild-type mice

embryo

abnormal placenta morphology ( J:234143 )

♀ • increase in placental adenosine levels

♀ • treatment with adenosine deaminase enzyme therapy reduces placental adenosine levels and ameliorates placental defects

abnormal placenta vasculature ( J:234143 )

♀ • placentas show disorganized and impaired vasculature in the labyrinthine zone

♀ • treatment with adenosine deaminase enzyme therapy ameliorates placental defects

small placenta ( J:234143 )

♀

decreased placenta weight ( J:234143 )

♀

hematopoietic system

increased dendritic cell number ( J:138722 )

• the number of proangiogenic CD11b^lowCD11c+ dendritic cells in the lungs is increased by 3-fold and they exhibit increased size compared to in wild-type mice

muscle

vascular smooth muscle hypertrophy ( J:231559 )

• thickening of the vascular smooth muscle wall in the lungs

• treatment with the ADORA2B antagonist GS-6201 reduces the thickening of the vascular smooth muscle wall

heart right ventricle hypertrophy ( J:231559 )

• mice develop right ventricle hypertrophy

• treatment with GS-6201 reduces right ventricle hypertrophy

increased vascular smooth muscle cell proliferation ( J:231559 )

• increase in proliferation of cells within the vascular wall of the lungs

respiratory system

abnormal lung vasculature morphology ( J:231559 )

• mice exhibit vascular remodeling in the lung

• increase in muscularization of vessels and a greater number of muscularized vessels are seen in the lung parenchyma

• treatment with GS-6201 inhibits the extent of muscularization but not the number of muscularized vessels

abnormal pulmonary alveolar system morphology ( J:231559 )

• mice show airspace enlargement

• treatment with the ADORA2B antagonist GS-6201reduces airspace enlargement

increased lung elastance ( J:231559 )

• lung elastance is increased

• treatment with GS-6201 inhibits the changes in lung function

increased airway resistance ( J:231559 )

• lung resistance is increased

• treatment with GS-6201 inhibits the changes in lung function

decreased lung compliance ( J:231559 )

• lung compliance is reduced

• treatment with GS-6201inhibits the changes in lung function

abnormal pulmonary gas exchange ( J:231559 )

• mice show decreased levels of arterial oxygen saturation compared with controls

• treatment with GS-6201 inhibits the decreased levels of arterial oxygenation; improves gas exchange in the lung