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A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys
Published on: December 2, 2014
Expression of Fraser syndrome genes in normal and polycystic murine kidneys
Larissa Kerecuk1, David A Long, Zahabia Ali
1UCL Institute of Child Health, London, UK.
Background:
Fraser syndrome (FS) features renal agenesis and cystic kidneys. Mutations of FRAS1 (Fraser syndrome 1)and FREM2 (FRAS1-related extracellular matrix protein 2)cause FS. They code for basement membrane proteins expressed in metanephric epithelia where they mediate epithelial/mesenchymal signalling. Little is known about whether and where these molecules are expressed in more mature kidneys.
Methods:
In healthy and congenital polycystic kidney (cpk)mouse kidneys we sought Frem2 expression using a LacZ reporter gene and quantified Fras family transcripts. Fras1 immunohistochemistry was undertaken in cystic kidneys from cpk mice and PCK (Pkhd1 mutant) rats (models of autosomal recessive polycystic kidney disease) and in wildtype metanephroi rendered cystic by dexamethasone.
Results:
Nascent nephrons transiently expressed Frem2 in both tubule and podocyte epithelia. Maturing and adult collecting ducts also expressed Frem2. Frem2 was expressed in cpk cystic epithelia although Frem2 haploinsufficiency did not significantly modify cystogenesis in vivo. Fras1 transcripts were significantly upregulated, and Frem3 downregulated, in polycystic kidneys versus the non-cystic kidneys of littermates. Fras1 was immunodetected in cpk, PCK and dexamethasone-induced cystepithelia.
Conclusions:
These descriptive results are consistent with the hypothesis that Fras family molecules play diverse roles in kidney epithelia. In future, this should be tested by conditional deletion of FS genes in nephron segments and collecting ducts.
Insights
Fraser syndrome (FS) genes FRAS1 and FREM2 are expressed in developing and mature kidney epithelia. While present in polycystic kidney disease models, their direct role in cyst formation requires further investigation.
Area of Science:
- Nephrology
- Developmental Biology
- Extracellular Matrix Biology
Background:
- Fraser syndrome (FS) is a genetic disorder characterized by renal agenesis and cystic kidneys.
- Mutations in FRAS1 and FREM2, which encode basement membrane proteins, are known causes of FS.
- These proteins are crucial for epithelial/mesenchymal signaling during kidney development, but their expression in mature kidneys is poorly understood.
Purpose of the Study:
- To investigate the expression patterns of Fras family genes (FRAS1, FREM2, FREM3) in healthy and polycystic kidney models.
- To explore the potential role of these genes in kidney cystogenesis.
Main Methods:
- Utilized a LacZ reporter gene to track Frem2 expression in mouse kidneys.
- Quantified Fras family transcripts in wildtype and polycystic kidney models (cpk mice, PCK rats).
- Performed Fras1 immunohistochemistry on cystic kidney samples and experimentally induced cysts.
Main Results:
- Frem2 expression was observed in nascent nephrons, maturing collecting ducts, and podocytes.
- Frem2 was present in cystic epithelia of cpk mice, but haploinsufficiency did not alter cystogenesis.
- Fras1 transcripts were upregulated, and Frem3 downregulated, in polycystic kidneys; Fras1 was detected in various cystic epithelia.
Conclusions:
- Fras family molecules exhibit diverse expression patterns in kidney epithelia, suggesting varied roles.
- Further research involving conditional gene deletion in specific nephron segments is warranted to elucidate their functions in kidney disease.
