Phenotypes Associated with This Genotype

Genotype
MGI:2683994

• Allelic Composition: Ada^tm1Mw/Ada^tm1Mw; Tg(PLADA)4118Rkmb/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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

Structural alterations in the thymus and spleen of Ada^tm1Mw/Ada^tm1Mw Tg(PLADA)4118Rkmb/0 mice

mortality/aging

postnatal lethality, complete penetrance ( J:73418 , J:234143 )

• 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

abnormal thymus corticomedullary boundary morphology ( J:73418 )

• with decreased cortical-medullary demarcation

small thymus ( J:73418 )

increased double-negative T cell number ( J:73418 )

• in thymus

anemia ( J:73418 )

increased granulocyte number ( J:73418 )

increased eosinophil cell number ( J:73418 )

increased macrophage cell number ( J:73418 )

decreased leukocyte cell number ( J:73418 )

decreased double-positive T cell number ( J:73418 )

• in both thymus and spleen

abnormal spleen red pulp morphology ( J:73418 )

• with decreased numbers of red blood cells and few megakaryocytes observed

small spleen ( J:73418 )

spleen hypoplasia ( J:73418 )

• lymphoid counts substantially reduced

decreased immunoglobulin level ( J:73418 )

immune system

abnormal thymus corticomedullary boundary morphology ( J:73418 )

• with decreased cortical-medullary demarcation

small thymus ( J:73418 )

increased double-negative T cell number ( J:73418 )

• in thymus

increased granulocyte number ( J:73418 )

increased eosinophil cell number ( J:73418 )

increased macrophage cell number ( J:73418 )

decreased leukocyte cell number ( J:73418 )

decreased double-positive T cell number ( J:73418 )

• in both thymus and spleen

abnormal spleen red pulp morphology ( J:73418 )

• with decreased numbers of red blood cells and few megakaryocytes observed

small spleen ( J:73418 )

spleen hypoplasia ( J:73418 )

• lymphoid counts substantially reduced

decreased immunoglobulin level ( J:73418 )

lung inflammation ( J:73418 )

• evidence of inflammatory cells, thickening and shedding of airway epithelium and occlusion of airways with mucous and cellular debris

renal/urinary system

renal/urinary system phenotype ( J:234143 )

♀N • proteinuria and kidney abnormalities are abolished

abnormal renal glomerulus morphology ( J:73418 )

• increased red blood cells within glomeruli

abnormal renal tubule morphology ( J:73418 )

• increased red blood cells within convoluted tubules

respiratory system

lung inflammation ( J:73418 )

• evidence of inflammatory cells, thickening and shedding of airway epithelium and occlusion of airways with mucous and cellular debris

tachypnea ( J:73418 )

• evident beginning at postnatal day 12 and progressively labored breathing until death

skeleton

abnormal costochondral joint morphology ( J:73418 )

• enlarged costochondral junctions

abnormal rib morphology ( J:73418 )

• severe rib curvature

endocrine/exocrine glands

abnormal thymus corticomedullary boundary morphology ( J:73418 )

• with decreased cortical-medullary demarcation

small thymus ( J:73418 )

cardiovascular system

cardiovascular system phenotype ( J:234143 )

♀N • hypertension is abolished

embryo

embryo phenotype ( J:234143 )

♀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