About   Help   FAQ
Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Adatm1Mw
targeted mutation 1, Maki Wakamiya
MGI:1857117
Summary 7 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Adatm1Mw/Adatm1Mw involves: 129S7/SvEvBrd MGI:3812473
hm2
Adatm1Mw/Adatm1Mw involves: 129S7/SvEvBrd * C57BL/6 MGI:2183043
hm3
Adatm1Mw/Adatm1Mw involves: 129S7/SvEvBrd * C57BL/6 * FVB/N MGI:2168183
cx4
Adatm1Mw/Adatm1Mw
Adora2btm1Dgen/Adora2btm1Dgen
Tg(Afp-ADA)#Xiay/0
involves: 129P2/OlaHsd * 129S7/SvEvBrd * C3H/HeJ * C57BL/6J MGI:5897419
cx5
Adatm1Mw/Adatm1Mw
Tg(Afp-ADA)#Xiay/0
involves: 129S7/SvEvBrd * C3H/HeJ * C57BL/6J MGI:5897391
cx6
Adatm1Mw/Adatm1Mw
Tg(PLADA)4118Rkmb/0
involves: 129S7/SvEvBrd * C57BL/6 MGI:2683994
cx7
Adatm1Mw/Adatm1Mw
Tg(PLFSADA)2465Rkmb/0
involves: 129S7/SvEvBrd * C57BL/6 * FVB/N MGI:2682599


Genotype
MGI:3812473
hm1
Allelic
Composition
Adatm1Mw/Adatm1Mw
Genetic
Background
involves: 129S7/SvEvBrd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adatm1Mw mutation (3 available); any Ada mutation (19 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• mice develop right ventricle hypertrophy
• treatment with GS-6201 reduces right ventricle hypertrophy

cellular
• fetuses from pregnant mutant females are smaller and weigh less

cardiovascular system
• 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
• placentas show disorganized and impaired vasculature in the labyrinthine zone
• treatment with adenosine deaminase enzyme therapy ameliorates placental defects
• 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
• mice develop right ventricle hypertrophy
• treatment with GS-6201 reduces right ventricle hypertrophy
• mice develop increased right ventricle systolic pressure
• treatment with GS-6201 reduces right ventricle systolic pressure
• mice exhibit hallmarks of pulmonary hypertension
• treatment with GS-6201 reduces the hallmarks of pulmonary hypertension
• increase in proliferation of cells within the vascular wall of the lungs

immune system
• the number of proangiogenic CD11blowCD11c+ dendritic cells in the lungs is increased by 3-fold and they exhibit increased size compared to in wild-type mice
• 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
• increase in placental adenosine levels
• treatment with adenosine deaminase enzyme therapy reduces placental adenosine levels and ameliorates placental defects
• placentas show disorganized and impaired vasculature in the labyrinthine zone
• treatment with adenosine deaminase enzyme therapy ameliorates placental defects

hematopoietic system
• the number of proangiogenic CD11blowCD11c+ dendritic cells in the lungs is increased by 3-fold and they exhibit increased size compared to in wild-type mice

muscle
• 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
• mice develop right ventricle hypertrophy
• treatment with GS-6201 reduces right ventricle hypertrophy
• increase in proliferation of cells within the vascular wall of the lungs

respiratory system
• 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
• mice show airspace enlargement
• treatment with the ADORA2B antagonist GS-6201reduces airspace enlargement
• lung elastance is increased
• treatment with GS-6201 inhibits the changes in lung function
• lung resistance is increased
• treatment with GS-6201 inhibits the changes in lung function
• lung compliance is reduced
• treatment with GS-6201inhibits the changes in lung function
• 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




Genotype
MGI:2183043
hm2
Allelic
Composition
Adatm1Mw/Adatm1Mw
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adatm1Mw mutation (3 available); any Ada mutation (19 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Hepatocyte abnormalities in Adatm1Mw/Adatm1Mw mice

cellular
• enlarged hepatocytes with karyomegaly as early as E16.5
• evident at E17.5

mortality/aging
• animals die at birth or shortly thereafter
• only 10% born with beating hearts, but these animals did not move

growth/size/body
• 15% smaller than littermates

homeostasis/metabolism
• pups born with beating hearts remained cyanotic until death a few hours later
• elevated levels of hepatocellular enzymes, aspartate aminotransferase (66%) and alanine aminotransferase (56%)
• dATP levels in fetal blood are elevated 2000-fold while ATP levels are decreased slightly

immune system
• decreased numbers of mature T lymphocytes

liver/biliary system
• livers have disorganized hepatic plates, resulting in isolated packets of cells
• evident at E17.5
• morphological changes in hepatocytes are seen as early as E16.5, including enlarged hepatocytes with karyomegaly, irregularly shaped nuclear envelopes, and a decrease in heterochromatin
• cytoplasm of hepatocytes has decreased amounts of glycogen and increased volume of rough ER
• hepatocytes lose their normal polyhedral shape and become round
• enlarged hepatocytes with karyomegaly as early as E16.5
• decrease in numbers of hepatocytes per lobule
• 29% smaller than littermates

hematopoietic system
• decreased numbers of mature T lymphocytes




Genotype
MGI:2168183
hm3
Allelic
Composition
Adatm1Mw/Adatm1Mw
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adatm1Mw mutation (3 available); any Ada mutation (19 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• mice exhibit increased corpus cavernosal smooth muscle relaxation in response to nerve stimulation
• mice exhibit erections lasting up to 72 hours that is associated with increased camp and cGMP production
• however, treatment with PEG-ADA corrects the observed priapism
• mice exhibit penile vascular damage, including marked intimal thickening with smooth muscle hypertrophy and endothelial swelling, and fibrosis subsequent to priapism




Genotype
MGI:5897419
cx4
Allelic
Composition
Adatm1Mw/Adatm1Mw
Adora2btm1Dgen/Adora2btm1Dgen
Tg(Afp-ADA)#Xiay/0
Genetic
Background
involves: 129P2/OlaHsd * 129S7/SvEvBrd * C3H/HeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adatm1Mw mutation (3 available); any Ada mutation (19 available)
Adora2btm1Dgen mutation (0 available); any Adora2b mutation (5 available)
Tg(Afp-ADA)#Xiay mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
N
• preeclampsia features seen in Adatm1Mw/Adatm1Mw Tg(Afp-ADA)#Xiay/0 dams, including hypertension are ameliorated

renal/urinary system
N
• preeclampsia features seen in Adatm1Mw/Adatm1Mw Tg(Afp-ADA)#Xiay/0 dams dams, including proteinuria and renal changes are ameliorated

embryo
• mice exhibit an increase in placental adenosine levels
• however, placental weight is increased and placental vasculature is more organized and uniform compared to Adatm1Mw/Adatm1Mw Tg(Afp-ADA)#Xiay/0 mice




Genotype
MGI:5897391
cx5
Allelic
Composition
Adatm1Mw/Adatm1Mw
Tg(Afp-ADA)#Xiay/0
Genetic
Background
involves: 129S7/SvEvBrd * C3H/HeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adatm1Mw mutation (3 available); any Ada mutation (19 available)
Tg(Afp-ADA)#Xiay mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice die by 3 weeks of age because hepatic production of ADA subsides during the first week following birth
• however, treatment with adenosine deaminase enzyme replacement therapy prevents this lethality and the phenotypes described are with mice that have been treated with the replacement therapy from birth

cellular
• fetuses from mutant pregnant females are smaller and weigh less

cardiovascular system
• pregnant mice show impaired placental vasculature and reduced CD31+ vessels in the placenta
• dams develop preeclampsia
• dams show an increase in mean systolic blood pressure late in pregnancy beginning on E15.5, which remains elevated through E17.5 and returns to normal by day 5 postpartum
• mean arterial pressure is elevated on E18.5 in dams

embryo
• pregnant mice exhibit elevated placental adenosine levels at E12.5 that remain elevated through E18.5
• pregnant mice show impaired placental vasculature and reduced CD31+ vessels in the placenta

homeostasis/metabolism
• urinary protein (ratio of albumin/creatinine) is elevated on E18.5 but not on E12.5, and this proteinuria is reduced to normal levels by postpartum day 7

renal/urinary system
• urinary protein (ratio of albumin/creatinine) is elevated on E18.5 but not on E12.5, and this proteinuria is reduced to normal levels by postpartum day 7
• swollen glomeruli with narrowed capillary and Bowmans spaces in pregnant mice
• pregnant mice show glomerular endotheliosis

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
pre-eclampsia DOID:10591 OMIM:189800
OMIM:609402
OMIM:609403
OMIM:609404
OMIM:614592
J:234143




Genotype
MGI:2683994
cx6
Allelic
Composition
Adatm1Mw/Adatm1Mw
Tg(PLADA)4118Rkmb/0
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adatm1Mw mutation (3 available); any Ada mutation (19 available)
Tg(PLADA)4118Rkmb mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Structural alterations in the thymus and spleen of Adatm1Mw/Adatm1Mw Tg(PLADA)4118Rkmb/0 mice

mortality/aging
• death by 3 weeks of age (J:73418)
• following birth and removal of the placenta, mice die within 3 weeks from severe pulmonary impairment due to excessive accumulation of adenosine (J:234143)
• however, treatment with adenosine deaminase enzyme replacement therapy prevents this lethality and the phenotypes described are with mice that have been treated with the replacement therapy from birth (J:234143)

hematopoietic system
• with decreased cortical-medullary demarcation
• in both thymus and spleen
• with decreased numbers of red blood cells and few megakaryocytes observed
• lymphoid counts substantially reduced

immune system
• with decreased cortical-medullary demarcation
• in both thymus and spleen
• with decreased numbers of red blood cells and few megakaryocytes observed
• lymphoid counts substantially reduced
• evidence of inflammatory cells, thickening and shedding of airway epithelium and occlusion of airways with mucous and cellular debris

renal/urinary system
N
• proteinuria and kidney abnormalities are abolished
• increased red blood cells within glomeruli
• increased red blood cells within convoluted tubules

respiratory system
• evidence of inflammatory cells, thickening and shedding of airway epithelium and occlusion of airways with mucous and cellular debris
• evident beginning at postnatal day 12 and progressively labored breathing until death

skeleton
• enlarged costochondral junctions
• severe rib curvature

endocrine/exocrine glands
• with decreased cortical-medullary demarcation

cardiovascular system
N
• hypertension is abolished

embryo
N
• placental adenosine levels are restored to normal levels, placental weights and vasculature are normal, and fetal weights from mutant dams are normal

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
adenosine deaminase deficiency DOID:5810 OMIM:102700
J:73418




Genotype
MGI:2682599
cx7
Allelic
Composition
Adatm1Mw/Adatm1Mw
Tg(PLFSADA)2465Rkmb/0
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Adatm1Mw mutation (3 available); any Ada mutation (19 available)
Tg(PLFSADA)2465Rkmb mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• no hepatocellular damage; rescued from perinatal lethality seen in homozygous mice
• rescue from severe, perinatally lethal respiratory distress seen in mice homozygous for Adatm1Mw





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
Citing These Resources
Funding Information
Warranty Disclaimer & Copyright Notice
Send questions and comments to User Support.
last database update
11/10/2020
MGI 6.16
The Jackson Laboratory