Phenotypes associated with this allele

• Allele Symbol: Tnfaip2^tm1.1Ohno
• Allele Name: targeted mutation 1.1, Hiroshi Ohno
• Allele ID: MGI:7564565
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnfaip2^tm1.1Ohno/Tnfaip2^tm1.1Ohno	C.Cg-Tnfaip2^tm1.1Ohno	MGI:7564569

Genotype
MGI:7564569

hm1

• Allelic Composition: Tnfaip2^tm1.1Ohno/Tnfaip2^tm1.1Ohno
• Genetic Background: C.Cg-Tnfaip2^tm1.1Ohno

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

renal/urinary system

albuminuria ( J:343202 )

• mice show a 2-fold increase in albuminuria at 6 weeks of age and an 8.5-fold increase at 24 weeks of age

abnormal glomerular capsule parietal layer morphology ( J:343202 )

• the number of CD44+ parietal epithelial cells (PECs) lying on the Bowmans capsule increase progressively with age

abnormal podocyte morphology ( J:343202 )

• podocyte injury (desmin staining and podocyte apoptosis) is seen as early as 6-10 weeks of age

podocyte foot process effacement ( J:343202 )

decreased podocyte number ( J:343202 )

• progressive reduction in podocin and synaptopodin expression and eventually in podocyte number

glomerulosclerosis ( J:343202 )

• focal glomerular sclerosis that worsens over time

• 18-week-old and 24-week-old mice show scarring involving 15% and about 25% of the glomeruli, respectively

• severity of scarring worsens progressively within individual glomeruli

• cuboidal CD44+ and Ki-67+ cells are seen in the tubules of older (18-week-old) mice

• however, macrophage infiltration and expression of CCL2 and TNF-alpha are unaltered within glomeruli and no IgM, C3, IgG, and IgA staining is seen indicating no inflammation

dilated nephron ( J:343202 )

renal cast ( J:343202 )

• cast formation is seen in tubules

abnormal kidney physiology ( J:343202 )

• glomeruli show an early and progressive reduction in both mtDNA copy number and expression of mitochondrial transcription factor/genes

• glomeruli mitochondrial membrane potential undergoes progressive reduction and mitochondrial oxidative stress is enhanced

• however, glomeruli show normal mitochondrial structure and mitochondrial mass is not altered

• however, no changes in mitochondrial membrane potential and TFAM expression are seen in renal tubular epithelial cells

• cells positive for both the PEC marker annexin A3 and CD44 are seen in the glomerular tuft indicating activated PECs

increased podocyte apoptosis ( J:343202 )

• 6-week-old podocytes show increased apoptosis

abnormal podocyte physiology ( J:343202 )

• tunneling nanotube-mediated mitochondrial transfer is almost abolished in mutant podocytes

• study of mitochondrial bioenergetics shows that basal and maximal oxygen consumption rate, ATP-linked respiration, and reserve capacity are reduced in podocytes, most likely due to alterations in oxidative phosphorylation as nonmitochondrial respiration and proton leak are unaltered

• low reserve capacity indicates that mitochondria function at their maximal capacity and are unable to meet any additional ATP demand

decreased creatinine clearance ( J:343202 )

• older mice exhibit a 40% reduction in creatinine clearance

homeostasis/metabolism

albuminuria ( J:343202 )

• mice show a 2-fold increase in albuminuria at 6 weeks of age and an 8.5-fold increase at 24 weeks of age

abnormal enzyme/coenzyme activity ( J:343202 )

• mice show an early and progressive increase in N-acetyl-beta-D-glucosaminidase activity

cellular

increased podocyte apoptosis ( J:343202 )

• 6-week-old podocytes show increased apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
focal segmental glomerulosclerosis		DOID:1312	OMIM:PS603278	J:343202