ENU Totally Explained

Everything about Enu totally explained

== N-ethyl-N-nitrosourea (ENU)==
ENU, also known as N-ethyl-N-nitrosourea (chemical formula C₃H₇N₃O₂), is a highly potent mutagen. For a given gene in mice, ENU can induce 1 new mutation in every 700 gametes. It is also toxic at high doses.
The chemical is an alkylating agent, and acts by transferring the ethyl group of ENU to nucleobases (usually thymine) in nucleic acids. Its main targets are the spermatogonial stem cells, from which mature sperm are derived.

Background of discovery of ENU as a mutagen

Bill Russell (1951) created a landmark in the field of mouse genetics by creating a specifically designed mouse strain, the T (test) stock that was used in genetic screens for testing mutagens such as radiations and chemicals. The T-stock mouse harbors 7 recessive, viable mutations affecting easily recognizable traits. At the Oak Ridge National Laboratory, Russell's initial goal was to determine the rate of inheritable gene mutations in the germ line induced by radiations. Thus he decided to use T-stock mice in order to define how often a set of loci could be mutated with radiations. Since the mutations in the T-stock mouse were recessive, the progeny would have a wild type phenotype (as a result of crossing a mutant [eg.s/smutant male] to a wild type female [+/+]). Thus with any progeny carrying a mutation induced by radiation at one of the 7 loci, would exhibit the mutant phenotype in the first generation itself. This approach, the specific locus test (SLT) allowed Russell to study a wide range of specific mutations and to calculate the mutation rates induced by radiations.
In addition to studying the effect of radiation for SLT, Russell et al. were also interested in studying the effect of chemical mutagens such as procarbazine and ethylnitrosourea for SLT. At that time, procarbazine was the most potent chemical mutagen known to cause a significant spermatogonial mutagenesis in an SLT, although at a rate one-third of that of X-rays. Russell's earlier mutagenesis work on Drosophila using diethylnitrosoamine (DEN) triggered them to use DEN for the SLT. However, DEN needs to be enzymatically converted into an alkylating agent in order to be mutagenic and probably this enzymatic activation wasn't sufficient in mammals. This could be illustrated by the extremely low mutation rate in mice given by DEN (3 in 60,179 offsprings). To overcome this problem, a new mutagen, N-ethyl N-nitrosourea (ENU), an alkylating agent, which doesn't need to be metabolised, was suggested to be used by Ekkehart Vegel to Russell et al. The ENU (250 mg/kg) induced mice underwent a period of sterility for 10 weeks. After recovery, 90 males were crossed to the T-stock females and 7584 pups were obtained.
To overcome the problem of initial period of sterility, the Russell group showed that instead of injecting one large dose of ENU, a fractionated dose (100mg/kg) on a weekly schedule permitted a total higher dose (300-400mg/kg) However it's also shown to cause GC->AT transitions..

2.It is known to induce point mutations, which implies that by mapping for the desired phenotype, the researcher can identify a single candidate gene responsible for the phenotype..

3.The point mutations are approximately are at 1-2 Mb interval and occur at an approximate rate of 1 per 700 gametes. Delta 1 is a ligand for the Notch receptor. A homozygous loss-of-function of Delta 1 (Dll1^lacZ/lacZ) is embryonically lethal. ENU-treated mice were crossed to Dll1^lacZ heterozygotes. 35 mutant lines were generated in G₁ of which 7 revealed modifiers of the Notch signaling pathway.

c. Sensitized screens In the case of genetic diseases involving multiple genes, mutations in multiple genes contributes to the progression of a disease. Mutation in just one of these genes however, might not contribute significantly to any phenotype. Such "predisposing genes" can be identified using sensitized screens. In this type of a screen, the genetic or environmental background is modified so as to sensitize the mouse to these changes. The idea is that the predisposing genes can be unraveled on a modified genetic or environmental background. Rinchik et al performed a sensitized screen of mouse mutants predisposed to Diabetic nephropathy. Mice were treated with ENU on a sensitized background of type-1 diabetes. These diabetic mice had a dominant Akita mutation in the insulin-2 gene (Ins2^Akita). These mice developed albuminuria, a phenotype that wasn't observed in the non-diabetic offsprings.Further Information

Get more info on 'Enu'.

External Link Exchanges

Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:

<a href="http://enu.totallyexplained.com">ENU Totally Explained</a>

Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned.