title: Novel candidate genes for impaired nephron development in a rat model with inherited nephron deficit and albuminuria.
abstract: Defects in nephrogenesis can have detrimental effects on cardiovascular and renal health in adult life. This is confirmed by observations in the Munich Wistar Frömter (MWF) rat that exhibits a congenital nephron deficit and renal failure with age. Here, we performed genome-wide transcriptome analysis in embryonic kidneys to identify candidate genes for the reduced nephron number in MWF. We compared MWF rats at embryonic day (E)15.5 with stage-matched spontaneously hypertensive rats (SHR) at E16. Microarray analysis revealed 311 transcripts representing 253 known genes with differential expression between MWF and SHR (fold change > +1.5 or < -1.5, respectively). Genes located on rat chromosome (RNO) 6 were of special interest because RNO6 carries genetic loci previously linked to the nephron deficit and renal damage in MWF. Differentially expressed genes located on RNO6 were further investigated by Real-time PCR including the late-stage of fetal kidney development, i.e. E19.0/E19.5, and week 4 of postnatal life when nephrogenesis is completed. Seven genes including Abcg5, Ab1-233, Efcab11, Fntb, Gpx2, Lrrn3, and Rtn1 were assigned on RNO6 and their differential expression was confirmed. Thus, we identified several genes that may act as crucial players in nephron development and are responsible for the nephron deficit in the MWF model.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, CharitéCenter 4 - Therapy and Research, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Herlan
authors.affiliation: Department of Clinical Pharmacology and Toxicology, CharitéCenter 4 - Therapy and Research, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Department of Clinical Pharmacology and Toxicology, CharitéCenter 4 - Therapy and Research, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Leonard
authors.initials: L
authors.lastname: Schulte
authors.affiliation: Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.affiliation: Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hübner
authors.affiliation: Department of Clinical Pharmacology and Toxicology, CharitéCenter 4 - Therapy and Research, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
mesh_terms: D000419:Albuminuria / Q000196:embryology* / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D008297:Male; D009399:Nephrons / Q000196:embryology* / Q000378:metabolism; D051381:Rats; D013045:Species Specificity
keywords: albuminuria; genetics; kidney; microarray; nephrogenesis; rat