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ENU, also known as N-ethyl-N-nitrosourea (chemical formula C3H6N3O2), is a highly potent mutagen in mice. It has a mutation rate of 1 new mutation (at a particular gene) per 700 gametes. It is also toxic in high doses. In biology, a mutagen (Latin, literally origin of change) is an agent that changes the genetic information (usually DNA) of an organism and thus increases the number of mutations above the natural background level. ... Mutations are permanent, sometimes transmissible (if the change is to a germ cell) changes to the genetic material (usually DNA or RNA) of a cell. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Gametes (in Greek: γαμέτες) —also known as sex cells, germ cells, or spores—are the specialized cells that come together during fertilization (conception) in organisms that reproduce sexually. ...
The chemical is an alkylating agent, and acts by transferring the ethyl group of ENU to nucleobases (mainly thymine) in nucleic acids. Its main target is the spermatogonial stem cells, from which mature sperm derive from. Alkylation is the transfer of an alkyl group from one molecule to another. ... Ethyl is a two-carbon substituent in organic chemistry. ... Nucleobases are the parts of RNA and DNA that are involved in pairing up (see also base pairs). ... Thymine, also known as 5-methyluracil, is a pyrimidine nucleobase. ... A nucleic acid is a complex, high-molecular-weight biochemical macromolecule composed of nucleotide chains that convey genetic information. ... Schematic diagram of a sperm cell, showing the (1) acrosome, (2) cell membrane, (3) nucleus, (4) mitochondria, and (5) flagellum (tail) A sperm cell, or spermatozoon ( spermatozoa) (in Greek: sperm = semen and zoon = alive), is the haploid cell that is the male gamete. ...
ENU is an alkylating agent (See Figure) that is a powerful mutagen in mouse spermatogonial stem cells, producing single locus mutation frequencies of 6 X 10-3 to 1.5 x 10-3, equivalent to obtaining a mutation in a single gene of choice in one out of every 175 to 655 gametes screened.
The analysis of 61 sequenced germline mutations from 24 genes reveals that ENU predominantly modifies A.T base pairs, with 44% A.T to T.A transversions, 38% A.T to G.C transitions, 8% G.C. to C.G transversions, 5% A.T to C.G transitions, and 2% G.C to T.A transitions (See Figure).
G1 animals, heterozygous for ENUmutagenized chromosomes and Re are mated to mice hemizygous for a yellow-tagged deletion.
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