All Phenotypes Magi2<tm1Key> MGI Mouse

premature death ( J:213553 )

• on a 129 genetic background, the median survival of homozygotes is 50 days, and all mice die by 3 months of age

• Background Sensitivity: on a mixed (129/B6) genetic background, the median survival is 169 days, and many of these mice live beyond 1 year of age

postnatal growth retardation ( J:213553 )

• homozygotes appear normal at birth and are born at expected Mendelian ratios but exhibit growth retardation within a few weeks after birth

absent glomerular endothelium fenestra ( J:213553 )

• by 4 weeks of age, the endothelium displays a mild loss of fenestrations

• however, the glomerular basement membrane is of normal thickness

increased urine protein level ( J:213553 )

• on a 129 genetic background, homozygotes display progressive proteinuria by 3 weeks of age

• Background Sensitivity: on a mixed (129/B6) genetic background, homozygotes show lower-grade proteinuria with variable age of onset

albuminuria ( J:213553 )

• homozygotes display a significant increase in the urine albumin/creatinine ratio as early as 10 days of age

tubulointerstitial nephritis ( J:213553 )

• at 5.5 weeks, interstitium shows early fibrosis with only chronic interstitial inflammation

• by 7 weeks of age, tubulointerstitium shows advanced chronic changes with chronic inflammation, tubular atrophy, and interstitial fibrosis

abnormal glomerular capsule parietal layer morphology ( J:213553 )

• at 5.5 weeks of age, all proliferative and crescentic lesions observed in mutant glomeruli are exclusively composed of activated (KI67-positive) parietal epithelial cells (PECs), indicating PEC activation and proliferation in response to rapid and severe podocyte loss; a marker for macrophages, CD68, is negative in the cellular crescents

abnormal podocyte morphology ( J:213553 )

• at 3 weeks of age, a mild reduction in the abundance of podocyte proteins synaptopodin and podocin is observed, consistent with podocyte injury and/or loss

• homozygotes develop a diffuse and progressive podocytopathy

podocyte foot process effacement ( J:213553 )

• by 4 weeks of age, homozygotes display severe podocyte injury with diffuse foot process effacement

abnormal podocyte slit diaphragm morphology ( J:213553 )

• at 10 days of age, nephrin protein levels are already profoundly reduced in mutant glomeruli, coinciding with the onset of proteinuria; in contrast, other podocyte proteins, such as podocin and CD2AP, are not altered by 18 days of age

• at 3 weeks of age, nephrin protein expression is almost undetectable in mutant glomeruli, coincident with CIN85 up-regulation

absent podocytes ( J:213553 )

• expression of podocyte marker synaptopodin is markedly reduced at 3 weeks and absent by 5.5 weeks in all glomeruli with extracapillary proliferations, indicating a complete loss of podocytes

podocyte hypertrophy ( J:213553 )

• by 4 weeks of age, several podocytes appear hypertrophic and exhibit long, thin extensions of their cell bodies

podocyte microvillus transformation ( J:213553 )

• by 4 weeks of age, homozygotes display microvillous transformation of the cell membrane

expanded mesangial matrix ( J:213553 )

• at 3 weeks of age, homozygotes show a mild increase of extracellular matrix accumulation in the mesangium without glomerular hypercellularity, while the tubulointerstitium appears normal

cortical renal glomerulopathies ( J:213553 )

• homozygotes exhibit an early-onset proliferative and non-inflammatory glomerulopathy that ultimately results in death from renal failure

glomerulosclerosis ( J:213553 )

• by 7 weeks, the majority of glomeruli are globally sclerosed

glomerular crescent ( J:213553 )

• by 5.5 weeks, most glomeruli appear severely injured, with a collapsed tuft and marked epithelial cell proliferations, in many cases resembling cellular or fibrocellular crescents; however, no glomerular inflammation or hypercellularity is observed

• by 7 weeks, the majority of glomeruli are globally sclerosed with focal fibrous crescents

renal interstitial fibrosis ( J:213553 )

• at 5.5 weeks, the tubulointerstitium shows mild interstitial fibrosis

renal tubule atrophy ( J:213553 )

• at 5.5 weeks, the tubulointerstitium shows mild tubular atrophy

renal cast ( J:213553 )

• at 5.5 weeks, all homozygotes display tubular protein casts; a few glomeruli are globally or segmentally hyalinized

• by 7 weeks of age, the vast majority of glomeruli are globally hyalinized or sclerosed

abnormal glomerular filtration barrier function ( J:213553 )

kidney failure ( J:213553 )

• homozygotes die of renal failure by 3 months of age

increased circulating creatinine level ( J:213553 )

• homozygotes exhibit elevated serum creatinine levels

increased blood urea nitrogen level ( J:213553 )

• homozygotes exhibit elevated blood urea nitrogen (BUN) levels