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Searching for the genetic basis and mechanism of nephrogenesis defects in the HSRA congenital solitary kidney rat
Author(s) -
Wang Xuexiang,
Johnson Ashley,
Guo Zibiao,
Jia Zhen,
Garrett Michael
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.665.9
Subject(s) - nephron , kidney , biology , kidney development , kidney disease , renal function , medicine , endocrinology , gene , genetics , embryonic stem cell
Our lab recently developed a unique rat model (HSRA rat) with 50‐75% of offspring developing with a single kidney. The HSRA model exhibits ~20% less nephrons in the remaining kidney (in addition to the loss of one kidney), early glomerular and kidney hypertrophy, and elevated single nephron GFR, leading to progressive kidney injury and decline in kidney function. The HSRA model is also highly susceptible to hypertension induced kidney injury. With a detailed understanding of the physiological mechanism of long‐term cardiovascular and renal hemodynamics, we now seek to establish the mechanism of nephron deficiency in the solitary kidney as well as identify the exact genetic basis leading to the failure of one kidney to develop. RNA sequencing of embryonic kidney isolated at key stages of nephrogenesis (E14.5, 15.5, and 16.5) between embryos exhibiting a single kidney and two‐kidney control identified genes/pathways that may explain decreased nephrons exhibited in the solitary kidney. A recent genome‐wide association study performed by others using the heterogeneous stock (HS) rat (progenitor of HSRA model) identified genomic loci on chromosome 4, 10, and 14 associated with the solitary kidney. Whole genome sequencing of the HSRA model is currently planned, which when combined with identified loci, will expedite identification of genes contributing to solitary kidney. In summary, the identification of the specific gene defect, modifier genes, and signaling pathways that lead to loss of one kidney and nephron deficiency in the remaining kidney will provide a mechanistic link between solitary kidney genotype and the development of kidney dysfunction exhibited by the HSRA.