Biomedical subjects

Kristopher Schwab

Publications and source records attributed to Kristopher Schwab.

3 recordsLinked to original sources

PubMed2006

Comprehensive microarray analysis of Hoxa11/Hoxd11 mutant kidney development.

The Hox11 paralogous genes play critical roles in kidney development. They are expressed in the early metanephric mesenchyme and are required for the induction of ureteric bud formation and its subsequent branching morphogenesis. They are also required for the normal nephrogenesis response of the metanephric mesenchyme to inductive signals from the ureteric bud. In this report, we use microarrays to perform a comprehensive gene expression analysis of the Hoxa11/Hoxd11 mutant kidney phenotype. We examined E11.5, E12.5, E13.5 and E16.5 developmental time points. A novel high throughput strategy for validation of microarray data is described, using additional biological replicates and an independent microarray platform. The results identified 13 genes with greater than 3-fold change in expression in early mutant kidneys, including Hoxa11s, GATA6, TGFbeta2, chemokine ligand 12, angiotensin receptor like 1, cytochrome P450, cadherin5, and Lymphocyte antigen 6 complex, Iroquois 3, EST A930038C07Rik, Meox2, Prkcn, and Slc40a1. Of interest, many of these genes, and others showing lower fold expression changes, have been connected to processes that make sense in terms of the mutant phenotype, including TGFbeta signaling, iron transport, protein kinase C function, growth arrest and GDNF regulation. These results identify the multiple molecular pathways downstream of Hox11 function in the developing kidney.

Animals↗

PubMed2004

Microarray analysis of focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a leading cause of chronic renal failure in children. Recent studies have begun to define the molecular pathogenesis of this heterogeneous condition. Here we use oligonucleotide microarrays to obtain a global gene expression profile of kidney biopsy specimens from patients with FSGS in order to better understand the pathogenesis of this disease. METHODS: We extracted RNA from renal biopsy samples of 10 patients with the diagnosis of FSGS and from 5 control kidney samples, and produced labeled cRNA for hybridization to Affymetrix human U133A microarrays. RESULTS: We identified a gene expression fingerprint for FSGS that contained 429 of 22,283 possible genes, each with a p < 0.01, using RMA normalization, Welch t test, and at least a 1.8-fold change in 5 of the 10 patients examined. We also found gene expression differences in samples from subsets of patients who had either nephrotic syndrome or renal insufficiency. This screen identified many genes and genetic pathways that have already been implicated in the pathogenesis of FSGS. In addition, we found changes in gene expression in genetic pathways that have not been studied in FSGS. CONCLUSIONS: Oligonucleotide DNA microarray analysis of renal biopsy specimens identified a gene expression fingerprint in samples from a heterogeneous population of patients with FSGS. The genes and genetic pathways identified in this study can be compared to results of similar studies of other diseases to examine specificity and used to study the pathogenesis of FSGS.

Adolescent↗

PubMed2003

A catalogue of gene expression in the developing kidney.

BACKGROUND: Although many genes with important function in kidney morphogenesis have been described, it is clear that many more remain to be discovered. Microarrays allow a more global analysis of the genetic basis of kidney organogenesis. METHODS: In this study, Affymetrix U74Av2 microarrays, with over 12,000 genes represented, were used in conjunction with robust target microamplification techniques to define the gene expression profiles of the developing mouse kidney. RESULTS: Microdissected murine ureteric bud and metanephric mesenchyme as well as total kidneys at embryonic day E11.5, E12.5, E13.5, E16.5, and adult were examined. This work identified, for example, 3847 genes expressed in the E12.5 kidney. Stringent comparison of the E12.5 versus adult recognized 428 genes with significantly elevated expression in the embryonic kidney. These genes fell into several functional categories, including transcription factor, growth factor, signal transduction, cell cycle, and others. In contrast, surprisingly few differences were found in the gene expression profiles of the ureteric bud and metanephric mesenchyme, with many of the differences clearly associated with the more epithelial character of the bud. In situ hybridizations were used to confirm and extend microarray-predicted expression patterns in the developing kidney. For three genes, Cdrap, Tgfbi, and Col15a1, we observed strikingly similar expression in the developing kidneys and lungs, which both undergo branching morphogenesis. CONCLUSION: The results provide a gene discovery function, identifying large numbers of genes not previously associated with kidney development. This study extends developing kidney microarray analysis to the powerful genetic system of the mouse and establishes a baseline for future examination of the many available mutants. This work creates a catalogue of the gene expression states of the developing mouse kidney and its microdissected subcomponents.

Animals↗