Navigation Links
Mouse can do without man's most treasured genes
Date:5/14/2008

ANN ARBOR, Mich.---The mouse is a stalwart stand-in for humans in medical research, thanks to genomes that are 85 percent identical. But identical genes may behave differently in mouse and man, a study by University of Michigan evolutionary biologists Ben-Yang Liao and Jianzhi Zhang reveals.

Their results, which have implications for the use of mouse models in studying human disease, appear in the current issue of the journal Proceedings of the National Academy of Sciences (PNAS).

"Everyone assumes that deletion of the same gene in the mouse and in humans produces the same phenotype (an observable trait such as presence or absence of a particular disease). That's the basis of using the mouse to study human disease," said Zhang, an associate professor of ecology and evolutionary biology. "Our results show that may not always be the case."

Zhang and his graduate student Liao focused their study on so-called essential genes---genes which, through their effects on survival or fertility, are necessary for organisms to reach sexual maturity and reproduce. They then homed in on 120 essential human genes for which the mouse has an identical counterpart that also has been studied. Next they consulted a database that catalogs the results of experiments in which the mouse equivalents of human genes are deleted, or "knocked out."

If those 120 essential human genes are also essential in the mouse, deleting any of them should result in infertility or death before reproductive age. But the database showed an unexpected discrepancy.

"To our surprise, 22 percent of the 120 human essential genes are nonessential in the mouse," Zhang said. "I expected there would be some, but I never expected the percentage to be so high."

Intrigued, the researchers wanted to understand why the "essentiality" of some genes has changed in the time since human and mouse last shared a common ancestor. Looking more closely at the protein products of the individual genes that are essential in humans but nonessential in the mouse, they discovered that a much higher than expected percentage are located in the vacuole, a sac-like cellular structure that functions as a garbage dump---but a highly important garbage dump.

"The main function of the vacuole is to contain and degrade cellular wastes and toxins," Zhang said. "In humans, the absence of vacuole proteins causes those wastes and toxins to accumulate, often leading to fatal neurological diseases."

The same thing happens in the mouse, but at a much later stage of life, often past reproductive age. As a result, "many of these vacuole proteins are not so 'essential' to the mouse," Zhang said. "Even without the proteins, the mouse can survive long enough to reproduce."

The researchers speculated that in the course of primate evolution, as life span increased and reproductive age was delayed, efficient waste management became increasingly important.

Additional results of their analysis support the idea. By developing an index that incorporated metabolic rate (a measure of how fast cellular waste products are generated) and reproductive age, and then using that index to compare human and mouse, the researchers determined that the total amount of waste produced per gram of body mass from birth to reproductive age is about 18 times higher for humans than for the mouse.

"Hence, waste management is much more important in humans than in the mouse for maintaining proper cellular functions until the time of reproduction," Zhang said. "And when a biological process becomes more important to a species, the genes involved in that process tend to become essential."

Zhang acknowledges that the study involved a relatively small number of genes, and he hopes that other researchers will be able to confirm the results as more information on human and mouse genes becomes available.

"If our sample is unbiased, our results will have some important implications," he said. "First, in many genome projects, people draw inferences about gene function by using information from other model organisms. We need to be careful doing this because we now know that a large fraction of the genes may have different functions or different importance in different species."

In addition, the results raise concerns about the widespread use of mouse models for studying human disease.

"Our study does not say that mouse models are useless," Zhang said. "Even for those genes that have changed essentiality, the mouse model may provide useful information. For example, it may tell us the molecular function of the gene, even if the gene's importance differs between species. But for some diseases, such as neurological diseases related to vacuole proteins, the phenotype is so different that it may be necessary to establish a primate model."


'/>"/>

Contact: Nancy Ross-Flanigan
rossflan@umich.edu
734-647-1853
University of Michigan
Source:Eurekalert

Related biology news :

1. Mouse study: When it comes to living longer, its better to go hungry than go running
2. Negligent, attentive mouse mothers show biological differences
3. Scientists successfully treat new mouse model of inflammatory bowel disease
4. Book is the first high-resolution digital mouse brain atlas designed for Web applications
5. Dissecting the genetic components of adaptation of E. coli to the mouse gut
6. CSHL scientists identify and repress breast cancer stem cells in mouse tissue
7. New chimeric mouse model for human liver diseases, drug testing
8. Looking through the eyes of a mouse, scientists monitor circulating cells in its bloodstream
9. Cancer-resistant mouse discovered
10. Immune cells promote blood vessel formation in mouse endometriosis
11. A computer for your mouse!
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... , June 27, 2016 Research and ... North America 2016-2020" report to their offering. ... North America to grow at a CAGR of ... been prepared based on an in-depth market analysis with inputs from ... prospects over the coming years. The report also includes a discussion ...
(Date:6/22/2016)... -- The American College of Medical Genetics and Genomics was once ... one of the fastest-growing trade shows during the Fastest 50 ... Las Vegas . Winners ... each of the following categories: net square feet of paid ... The 2015 ACMG Annual Meeting was ranked 23 out of ...
(Date:6/22/2016)... LOS ANGELES , June 22, 2016 ... of identity management and verification solutions, has ... cutting edge software solutions for Visitor Management, ... ® provides products that add functional ... The partnership provides corporations and venues with ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016 Houston Methodist Willowbrook Hospital ... Sports Association to serve as their official health ... Methodist Willowbrook will provide sponsorship support, athletic training ... association coaches, volunteers, athletes and families. ... Sports Association and to bring Houston Methodist quality ...
(Date:6/23/2016)... ... , ... Supplyframe, the Industry Network for electronics hardware design ... Located in Pasadena, Calif., the Design Lab’s mission is to bring together inventors ... and brought to market. , The Design Lab is Supplyframe’s physical representation of ...
(Date:6/23/2016)... 23, 2016 Andrew ... http://doi.org/10.17925/OHR.2016.12.01.22 Published recently in ... journal from touchONCOLOGY, Andrew D Zelenetz , ... cancer care is placing an increasing burden on ... biologic therapies. With the patents on many biologics ...
(Date:6/23/2016)... 2016  Amgen (NASDAQ: AMGN ) today ... life sciences incubator to accelerate the development of ... space at QB3@953 was created to help high-potential life ... many early stage organizations - access to laboratory infrastructure. ... launched two "Amgen Golden Ticket" awards, providing each winner ...
Breaking Biology Technology: