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Abstract: SA-PO366

Podocyte-Specific Crb2 Knockout Mice Cause Proteinuria

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Katayama, Kan, Mie university graduate school of medicine, Tsu, Japan
  • Ito, Yugo, Karolinska Institute, Stockholm, Sweden
  • Ito, Masaaki, Mie university graduate school of medicine, Tsu, Japan
Background

Crumbs 2, Crb2 is known to be expressed in the podocytes. Knockdown of crb2 caused cardiac edema in zebrafish and full knockout of Crb2 resulted in embryonic lethality. Moreover, there have been reports of steroid-resistant nephrotic syndrome by CRB2 mutations. However, its precise mechanism is still elusive.

Methods

We generated conditional Crb2 floxed mice that possessed loxP sites flanking exon 7 and 8. Podocyte-specific Crb2 knockout mice were generated by breeding Crb2 conditional knockout mice with NPHS2-Cre mice. Urine, blood, and renal histology were examined in NPHS2-Cre or Crb2 flox/flox or NPHS2-Cre & Crb2 flox/flox mice.

Results

NPHS2-Cre & Crb2 flox/flox mice showed massive proteinuria at two or six months of age compared to NPHS2-Cre mice or Crb2 flox/flox mice. Blood urea nitrogen or serum creatinine at two months of age was comparable among the three groups. Although renal histology at two months of age was also comparable among the three groups, glomerular sclerotic indices of NPHS2-Cre & Crb2 flox/flox mice at six months of age were significantly higher than those of NPHS2-Cre mice or Crb2 flox/flox mice.

Conclusion

Knockout of Crb2 in the podocytes might play an important role in developing proteinuria.