All Phenotypes Tns1<tm1Efu> MGI Mouse

decreased renal plasma flow rate ( J:39202 )

• pale kidney color suggests that fluid flow through the kidneys is compromised

tubulointerstitial nephritis ( J:39202 )

• affected kidneys display signs of focal interstitial inflammatory infiltrates

• homozygotes exhibit a slow, progressive kidney degeneration with a variable onset time

• although ageing homozygotes generally display more severe kidney defects, some mice older than 6 months only show mild cystic defects

• in severe cases, the cortex and medulla are so compressed that mutant kidneys appear nearly empty

kidney cyst ( J:39202 )

• mutant kidneys show variable cystic defects, ranging from extremely dilated cysts in the cortex and medulla in severely affected organs, to small cysts in the cortex in less affected organs

• most small cysts are derived from an expansion of the lumen of proximal tubules

• very small cysts can often be detected as early as 1-2 weeks after birth

• kidney cysts are prevalent even in homozygotes with normal blood analysis

kidney cortex cyst ( J:39202 )

• kidney cortex cysts range from extremely dilated to small, and often contain amorphous, noncellular materials, referred to as "casts"

• in cystic areas of the cortex, cell-matrix junctions are disrupted and tubule cells lack polarity; in contrast, noncystic areas display normal cell-matrix junctions

enlarged kidney ( J:39202 )

• mutant kidneys are often slightly larger than age-matched wild-type kidneys

abnormal kidney cortex morphology ( J:39202 )

• unlike wild-type kidneys which always display a dark reddish brown cortex, mutant kidneys show a less prominent color distinction between the cortex region and the lighter medulla

increased glomerular capsule space ( J:39202 )

• many mutant glomeruli exhibit enlarged Bowman's spaces

abnormal renal glomerulus morphology ( J:39202 )

• mutant glomeruli are surrounded by enlarged cuboidal epithelial cells with a prominent cytoplasm, rather than the normal thin flattened epithelia, barely visible in control glomeruli

• gross glomerular defects are often not observed until the adult stage

• however, neither fusions of foot processes nor separations of podocytes from their underlying basement membranes are observed

glomerulosclerosis ( J:39202 )

• in severely affected regions, signs of focal segmental glomerular sclerosis are observed

• in highly abnormal regions, the glomeruli are thickened and appear to contain extracellular depositions

abnormal kidney pelvis morphology ( J:39202 )

• in many mutant kidneys, the renal pelvis opening is significantly enlarged

• an enlarged renal pelvis space can often be detected as early as 2 weeks after birth

abnormal proximal convoluted tubule morphology ( J:39202 )

• in severely affected kidney regions, microvilli are largely deteriorated, mitochondria are less organized and less abundant, and the basal membrane shows fewer invaginations; many cells show abnormalities in cell shape, and the epithelium appears to be less polarized

• in mildly affected areas, the cuboidal epithelium of proximal tubules is polarized and ultrastructurally normal, with numerous microvilli on the apical surface; fewer undulations of the basal membrane are occasionally observed

dilated proximal convoluted tubule ( J:39202 )

• in mildly affected kidneys, dilated tubules are concentrated in the kidney cortex

• most dilated tubules display residual microvilli, exclusive to the proximal tubules of the kidney

renal cast ( J:39202 )

• kidney cortex cysts often contain amorphous, noncellular materials, referred to as "casts"

granular kidney ( J:39202 )

• mutant kidneys display a rough and granular surface, usually by ~4-8 weesk after birth

kidney degeneration ( J:39202 )

• homozygotes exhibit a slow, progressive kidney degeneration with a variable onset time

pale kidney ( J:39202 )

• mutant kidneys are uniformly pale, ranging from brown to light yellow, at all ages studied

kidney failure ( J:39202 )

• only 3 of 44 homozygotes (18 wk, 8 mo, and 9 mo of age) became visibly ill in a manner that might be consistent with renal failure

• all remaining homozygotes appeared clinically normal

reduced female fertility ( J:39202 )

• in 14 matings of homozygous females and males, only nine produced offspring

decreased litter size ( J:39202 )

• crosses between homozygous females and males yield an average litter size of only 3 pups, whereas crosses between homozygous males and either wild-type or heterozygous females produce normal litters, ranging from 7 to 9 pups

weakness ( J:39202 )

• homozygotes become progressively frail because of bilateral kidney abnormalities

• homozygotes with overt signs of weakness show signs of kidney failure and contain multiple large cysts in the proximal kidney tubules