Introduction: ADPKD Research

This web page was produced as an assignment for bioinformatics at Samford University

My research is focusing on autosomal dominant polycystic kidney disease (ADPKD) and the animal models used to study the behavior of the disease.

ADPKD manifests itself in two major ways. First, autosomal dominant polycystic kidney disease type 1 (PKD1) which is caused by mutations within the gene that codes for the protein polycystin-1 [3]. These mutations account for 85 percent of people that are diagnosed with ADPKD [1].

The remaining 15 percent accounts for people that have autosomal dominant polycystic kidney disease type 2 (PKD2) [4]. This type of the disease is caused by mutations within the gene coding for the protein polycystin-2 [2].

Together the two proteins work to maintain tubular function, cell growth and division, cell migration, and interactions with other cells. These cells are pivotal for long-term renal health. The interaction of polycystin-1 and polycystin-2 in the renal tubules promotes normal development and function of the kidneys [1][2].

Although the two proteins work together, they do not have the same function.

  • Polycystin-1 is a transmembrane protein that interacts with other proteins, lipids, carbohydrates outside of the cell and receives signals which help the cell respond to its environment [1]. When a signal binds to polycystin-1, it interacts with polycystin-2 to create a cascade of chemical reactions within the cell [1].
  • Polycystin-2 is a protein that is regulated by polycystin-1 which serves as a transport channel for positively charged calcium ions [2]. This influx of ions causes chemical reactions within the cell needed to help the cell respond to the environment [2].
Some of the functions of both Polycystin-1 and Polycystin-2 are known, however their exact functions are not well understood. Also it is not understood as to why the lack of one of these two proteins causes so much damage in ADPKD positive patients.
Both genes have been sequenced however PKD1 has the presence of many pseudogenes directly upstream of the actual gene. The presence of these pseudogenes makes it difficult to sequence the true amino acid sequence as well as determine mutations for the gene [6].
Those with PKD2 manifest similar symptoms as those with PKD1 [1] [2]. The two genes are not linked. For symptoms to arise, a patient needs only one of the genes to be mutated [5]. This fact was particularly interesting because upon further research I discovered that the reason that these two proteins are not linked is due to the location of their corresponding genes. The gene for polycystin-1 is located on chromosome 16, whereas the gene for polycystin-2 is located on chromosome 4 [3][4].
Since the genes are separate, not linked, and possess different functions, it could be possible that they need to be studied separately. Typically the mouse has been used as animal model for studying the protein/gene behaviors in both types (there have been studies with the rat, feline, and zebrafish version of the genes, but the principal model found is the mouse model) [3] [4].
Is it possible though, that the genes since separate, are different enough that a separate animal model should be used?

By analyzing the human gene sequences along with multiple animal sequences often used as animal models, I hope to determine whether or not a certain animal model should be used for researching/examining both types of the disease or a specific animal model for each type.

For more information about the methods I used for my research, click here.

References:

Literature cited:

[1].”PKD1.” – Polycystic Kidney Disease 1 (autosomal Dominant). Web. 8 May 2012. <http://ghr.nlm.nih.gov/gene/PKD1&gt;.

[2]. “PKD2.” – Polycystic Kidney Disease 2 (autosomal Dominant). Web. 8 May 2012. <http://ghr.nlm.nih.gov/gene/PKD2&gt;.

[3].”OMIM Entry – *601313 – POLYCYSTIN 1; PKD1.” OMIM Entry – *601313 – POLYCYSTIN 1; PKD1. NCBI. Web. 3 May 2012. <http://omim.org/entry/601313?search=pkd1&gt;.

[4].”OMIM Entry – *173910 – POLYCYSTIN 2; PKD2.” OMIM Entry – *173910 – POLYCYSTIN 2; PKD2. NCBI. Web. 3 May 2012. <http://omim.org/entry/173910&gt;.

[5]. “OMIM Entry – #173900 – POLYCYSTIC KIDNEY DISEASE 1; PKD1.” OMIM Entry – #173900 – POLYCYSTIC KIDNEY DISEASE 1; PKD1. NCBI. Web. 3 May 2012. <http://omim.org/entry/173900&gt;.

[6]. Rizk, D., & Chapman, A. (2008). Treatment of autosomal dominant polycystic kidney disease (adpkd): the new horizon for children with adpkd.Pediatric Nephrology, 23(7), 1029-1036. Retrieved from http://web.ebscohost.com.ezproxy.samford.edu/ehost/pdfviewer/pdfviewer?sid=f987e508-893f-453e-be85-9fba7934f29f@sessionmgr110&vid=8&hid=126

Graphics cited:

[1].”PKD1.” – Polycystic Kidney Disease 1 (autosomal Dominant). Web. 8 May 2012. <http://ghr.nlm.nih.gov/gene/PKD1&gt;.

[2]. “PKD2.” – Polycystic Kidney Disease 2 (autosomal Dominant). Web. 8 May 2012. <http://ghr.nlm.nih.gov/gene/PKD2&gt;.

May 9, 2012

Jfleming@samford.edu

BIO 306

Samford University

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