Phenotypes Associated with This Genotype

Genotype
MGI:6458735

• Allelic Composition: Tg(Thy1/THY1)T6Gsv/0
• Genetic Background: involves: C57BL/10 * CBA

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

renal/urinary system

albuminuria ( J:294728 )

• mice injected with an anti-Thy1^a (Thy1.1) mAb develop albuminuria; persistence of albuminuria is dose dependent

abnormal glomerular capsule parietal layer morphology ( J:294621 )

• parietal epithelial cells show vacuolization and detachment at day 1 of anti-Thy1.1 mAb injection

• parietal epithelial cells are activated with enlarged nuclei and prominent nucleoli at days 6 and 7 post anti-Thy1.1 mAb injection

abnormal glomerular capsule space morphology ( J:294621 )

• glomeruli show an increase of epithelial cells in Bowman's space at days 6 and 7 post anti-Thy1.1 mAb injection

increased glomerular capsule space ( J:294621 )

• enlarged Bowman's space due to collapse of the glomerular tuft at day 1 of anti-Thy1.1 mAb injection, indicating ischemia

abnormal podocyte morphology ( J:294621 )

abnormal podocyte foot process morphology ( J:294728 )

• the number of foot processes per 10 um glomerular basement membrane decreases over time in anti-Thy1^a (Thy1.1) mAb injected mice

• however, no podocyte detachment of denudation of the glomerular basement membrane or changes in glomerular basement membrane thickness are seen at 10 min or 8 hours after anti-Thy1^a (Thy1.1) mAb injection

podocyte foot process effacement ( J:294621 )

• global podocyte alterations with foot process effacement and mirocivllius transformation is seen at days 1 and 3 post anti-Thy1.1 mAb injection

• however, podocyte detachment or areas of denuded glomerular basement membrane are not seen

abnormal podocyte slit junction morphology ( J:294728 )

• the diameter of remaining slit pores is decreased in anti-Thy1^a (Thy1.1) mAb injected mice

podocyte hypertrophy ( J:294621 )

• affected glomerular segments show hypertrophic podocytes, with extensive vacuolization, resorption droplets, and formation of pseudocysts at days 6 and 7 post anti-Thy1.1 mAb injection

podocyte vacuoles ( J:294621 )

• affected glomerular segments show hypertrophic podocytes, with extensive vacuolization at days 6 and 7 post anti-Thy1.1 mAb injection

abnormal renal glomerulus morphology ( J:294621 )

• collapse of the glomerular tuft at day 1 of anti-Thy1.1 mAb injection

• glomeruli show segmental collapse of the capillary tuft space at days 6 and 7 post anti-Thy1.1 mAb injection

abnormal glomerular mesangium morphology ( J:294621 )

• mild mesangial hypercelluarity is sporadically seen at days 6 and 7 post anti-Thy1.1 mAb injection

glomerulosclerosis ( J:294621 , J:294728 )

• mice injected with an anti-Thy1^a (Thy1.1) mAb develop focal segmental glomerulosclerosis (FSGS) lesions within 3 weeks (J:294621)

• focal segmental glomerulosclerosis lesions are first seen at days 6 and 7 post anti-Thy1.1 mAb injection, with tuft adhesions to Bowman's capsule (J:294621)

• FSGS lesions resemble the collapsing variant of human FSGS (J:294621)

• FSGS lesions, with tuft adhesions to Bowman's capsule, are seen in 11% and 26% of glomeruli at days 6 and 7 post anti-Thy1.1 mAb injection, respectively (J:294621)

• at day 21 post anti-Thy1.1 mAb injection, the percentage of glomeruli with lesions does not increase but the lesions are more advanced, showing a high degree of extracellular matrix accumulation which leads to the formation of segmental or global scars (J:294621)

• tubular lumens exhibit many hyaline protein casts at day 1 of anti-Thy1.1 mAb injection (J:294621)

• mice injected with an anti-Thy1^a (Thy1.1) mAb develop focal glomerulosclerosis (J:294728)

renal glomerular synechia ( J:294621 )

• adhesions (continuity of extracellular matrix (ECM) between the capillary tuft and Bowmans capsule) form by thin strands of ECM that are located in between the epithelial cells in Bowman's space at days 6 and 7 post anti-Thy1.1 mAb injection

abnormal renal tubule morphology ( J:294728 )

• mice injected with an anti-Thy1^a (Thy1.1) mAb exhibit protein casts in distal tubules and collecting ducts already at 10 min after anti-Thy1^a (Thy1.1) mAb administration

• 8 hours after anti-Thy1^a (Thy1.1) mAb injection, protein casts are seen in all types of tubules and in glomeruli and proximal tubules exhibit a large number of resorption vacuoles and damaged cells

abnormal proximal convoluted tubule morphology ( J:294621 )

• proximal tubular epithelial cells exhibit damage at day 1 of anti-Thy1.1 mAb injection

dilated renal tubule ( J:294728 )

• mice injected with an anti-Thy1^a (Thy1.1) mAb exhibit dilated tubules

renal ischemia ( J:294621 , J:294728 )

• enlarged Bowman's space due to collapse of the glomerular tuft at day 1 of anti-Thy1.1 mAb injection, indicating ischemia (J:294621)

• glomeruli are no longer ischemic at day 3 post anti-Thy1.1 mAb injection (J:294621)

• glomeruli become increasingly ischemic after anti-Thy1^a (Thy1.1) mAb injection, leading to an enlarged Bowman's space due to the collapse of the glomerular tuft (J:294728)

oliguria ( J:294728 )

• mice injected with a high dose (2000 ug) of anti-Thy1^a (Thy1.1) mAb exhibit very low urine volumes

hematopoietic system

increased neutrophil cell number ( J:294621 )

• endocapillary neutrophils are sporadically seen in the kidney at days 6 and 7 post anti-Thy1.1 mAb injection

abnormal mononuclear cell morphology ( J:294621 )

• mononuclear cells are sporadically seen in the kidney at days 6 and 7 post anti-Thy1.1 mAb injection

increased macrophage derived foam cell number ( J:294621 )

• endocapillary foam cells are sporadically seen in the kidney at days 6 and 7 post anti-Thy1.1 mAb injection

homeostasis/metabolism

albuminuria ( J:294728 )

• mice injected with an anti-Thy1^a (Thy1.1) mAb develop albuminuria; persistence of albuminuria is dose dependent

immune system

increased neutrophil cell number ( J:294621 )

• endocapillary neutrophils are sporadically seen in the kidney at days 6 and 7 post anti-Thy1.1 mAb injection

abnormal mononuclear cell morphology ( J:294621 )

• mononuclear cells are sporadically seen in the kidney at days 6 and 7 post anti-Thy1.1 mAb injection

increased macrophage derived foam cell number ( J:294621 )

• endocapillary foam cells are sporadically seen in the kidney at days 6 and 7 post anti-Thy1.1 mAb injection

cellular

increased macrophage derived foam cell number ( J:294621 )

• endocapillary foam cells are sporadically seen in the kidney at days 6 and 7 post anti-Thy1.1 mAb injection

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
focal segmental glomerulosclerosis		DOID:1312	OMIM:PS603278	J:294621 , J:294728