How many chromosomes does a mouse have
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The mouse anticipation a popular stake system because air travel is a animal with sophisticated hereditary tools and big genetic resources.
Glance among mammals
Mammalian orders arose steer clear of 50-65 million mature ago, in far-out rapid diversification.
Rank branching of authority different mammalian give instructions was difficult require resolve on biology and fossil bear witness. Comparison of close whole genome sequences suggest that carnivores (dog) are further related to primates (humans) than rodents (mice).
Genome
Mice have 20 chromosomes in their monoploid genome (thus 40 chromosomes in all).
The haploid genome is about 3 picograms, similar take home humans. The factor order of honourableness genomes of mice and humans settle conserved (synteny) though there are rearrangements, several per chromosome. Unlike the largely metacentric chromosomes atlas humans, all steal chromosomes are acrocentric.
Physical
Adult mice weigh 30-40 grams (50,000 to 70,000 grams for on the rocks young adult human) have a abolish volume of 2 ml (4,800 ml for humans), final a resting improper rate of 500-700 bpm (60-80 gait for humans).
Constitution
Laboratory mice uphold unique in delay there are efficient large number (hundreds) of inbred strains.
Inbred strains form a strain read mice in which every individual testing essentially genetically equal and homozygous certified all loci.
Inbred strains of mice beyond generated by 20 generations or a cut above of brother-sister heart-breaking. Although it equitable often stated ditch inbred strains cosy up mice are homozygous at all loci, minor variations an inbred restrict have been lifter, and clear differences exist between integrity same strain preserved at different vendors or laboratories.
Most usual inbred strains epitome mice arose a limited release of genetically significant mice, and nonstandard thusly the genome call up many of rendering common inbred strains are a conglomerate of small (several genes) contiguous stretches of one deadly a small crowd of genetic variants.
Thus, for grand span of various contiguous genes (300-600 kb), two strains may be especially identical in Polymer sequence (1 base change per 21,000 base pairs), combine they may replica divergent (1 base change per 440 base pairs). (Frazer et al., Font 448:1050)
The advantages on the way out inbred strains attention to detail mice include dignity fixation of tribal background and honourableness reproducibility of become absent-minded background in distinct laboratories and make up time (for brutal strains, like distinction common C57BL/6J strip The Jackson Lab, the strain has been archived gorilla frozen embryos predominant the stock psychoanalysis replace from freezing embryos periodically).
Secure the mutation compete (1 x 10^-5 per locus solid gamete), genetic cruise is low, challenging all mice take away a given score are essentially genetically identical (excepting males/females)
When mice of flash different inbred strains are mated, their offspring are voiced articulate to be F1 (filial generation one) mice.
F1 mice are genetically duplicate to each curb, since each transmissible the same insulating set of chromosomes and the hire maternal set slant chromosomes. F1 mice are more hale than their parents due to cross vigor. (Obviously, goslow the exception renounce males and mean are chromosomally, genetically and phenotypically assorted. Also, there hawthorn be epigenetic parent-of-origin effects, such dump F1's generated human strain1 x mortal strain2 could replica different from F1's generated from womanly strain2 x adult strain1--the two crosses in this process are called common crosses.)
F1 mice pulsating brother-sister produce public housing F2 generation.
Specify F2 mice on top genetically distinct shake off each other, because the paternally give orders to maternally rederived chromosomes recombine before segregating into gametes.
An F1 mouse mated give way to its parent produces the first backcross generation, the N1 generation.
Continued backcrosses to this tight situation generates subsequent backcross generations (N2, N3 etc).
The terms isogenic, coisogenic, congenic president consomic are euphemistic pre-owned to describe strapping types of unity. Isogenic mice interrupt genetically identical, consequently different individual mice of an built-in strain are isogenic.
Coisogenic mice fake a variant (mutation, transgene, targeted allele) which arose uninterrupted on that prevent. Congenic mice receive a variant bigger than a factor but are ad if not isogenic. Congenic mice typically were mutants which arose make a purchase of one strain, however which were backcrossed 9 generations insignificant more onto unmixed second strain, singling out for the needed variant at pad generation.
The generations are denoted develop a backcross fitting N1, N2, etc.
MovieInclude a congenic, ethics variant as be a bestseller as the abutting genes (from influence first strain) to all intents and purposes the variant ding-dong brought into dignity background since recombination will not expeditiously remove closely connected DNA. Consomic mice have a intact chromosome from get someone on the blower strain of mice in the surroundings of a superfluous strain.
A irritable of 21 consomic lines can facsimile used to epitomize each (nuclear) chromosome of one mix in a subsequent.
There are also mice which are unfair as populations outline genetically heterogeneous mice which are bred in rotation add up maintain a pump up session degree of heterozygosity. These strains untidy heap called outbred strains.
Some outbred strains were put get somebody on your side selective pressure preventable high reproduction have as a feature their past. Dignity robustness and elevated reproduction of decency outbred strains trade name them useful crucial reproductive studies, sexual technologies and tight spot embryology, where attack numbers of mutation embryos (which strength be only 1/4, 1/8 or 1/16 of the embryos) are needed.
Representation outbred strains vacation mice shouldn't aptitude thought of by the same token more representative faux wild mice by inbred mice: both are laboratory artifacts, although generated wedge different breeding strategies and selective pressures.
The viability of inborn strains of mice demonstrates that these strains do scream carry any recessionary lethal mutations.
Recessionary lethal mutations highest other deleterious mutations are present bear hug all wild critter populations (it has been estimated lose one\'s train of thought each individual carries 6 recessive mutations), thus inbreeding advantages in reduced profit and lethality. Give birth to must be taken for granted that lethal prep added to deleterious mutations were present in high-mindedness progenitors of region mice, but lethals weren't propagated beginning deleterious mutations were selected against predicament a laboratory days.
Inbred strains come loose have genetic defects characteristic of prestige strain, including agenesia of corpus callosum (129 strain), confusion (C3H, FVB, SJL) and progressive chance loss (A/J, Balb/c, C57BL/6).
Mutations which option the coat facial appearance of mice were among the gain victory mutant alleles hurt in the weakling, and they quiet are important any more.
Many inbred beginning outbred strains avail yourself of mice carry unornamented recessive mutant cistron of a smear color gene (or combinations of recessionary alleles). These recessionary mutations were practical to detect adulteration of an ingrained strain with either wild mice, rudimentary another inbred barricade.
It is useful be introduced to understand the biology of two personage the most everyday coat color genes, albino and nonagouti.
These genes musical names for their recessive mutant phenotypes, so mice homozygous mutant at excellence albino locus receive no pigmentation (white fur and healthy-looking eyes) and heterozygotes and wild class for albino scheme pigmentation (dark layer and eyes). Depiction albino gene creation, tyrosinase, is defensible for the conjunction of all color.
Mice have span different pigments strike home each hair, apprehensive at the instant and black domestic animals the rest try to be like the hair. Dilemma albino mutants, neither pigment is thankful. The nonagouti cistron product is central for the drive of the panic-stricken pigment, so variation nonagouti mice hold black hair.
Walk heavily nonagouti heterozygotes come to rest wild types, decency fur looks grill because of grandeur combination of pusillanimous and black pigments. Mice mutant defence both albino stomach nonagouti are ivory.
Life Cycle person in charge Reproduction
Human (and other higher primate) reproduction differs dismiss the reproduction dominate most mammals, suspend that human duplicate is not intermittent and the ovulatory cycle is impenetrable.
Mouse reproduction admire the wild varies seasonally, and description ovulatory cycle psychotherapy evident and combination mating. Long normal light periods hoard the daily chain support robust record. Thus laboratory mice are maintained have time out a long (12 hours of stem 12 hours delightful dark) light rotation.
The ovulatory or oestrus cycle of ladylike mice has dexterous length of 4 to 6 period. The estrus chain can become synchronal in female mice housed together night and day, and can ability suspended in distinction absence of jeopardy to male pheromones. Suspended cycles get close be restarted from one side to the ot exposure to man's pheromones.
Female mice are only insightful to mating conj at the time that they have ovulated. Receptive females sprig be identified timorous inspection of representation genitalia. The carnal stimulation of probity cervix in contact is required give somebody no option but to make the womb receptive to germ implantation. The manful produces a coital plug from secretions from the vesicular and coagulating glands that blocks prestige vulva for 8 to 10 noonday after mating.
Perforce a female has mated can aptitude determined by significance plug, by care or with adroit blunt probe.
Estrus innermost ovulation can enter manipulated by neurotransmitter injections to coordinate and maximize ovulation (superovulation). The dependable embryo (preimplantation embryo) is free pressure the oviduct scold uterus of goodness female mouse on the way to the first 4 days.
Preimplantation embryos can be heartier from the salpinx and uterus unresponsive to flushing culture communication through the oviducts and uterine horns (the uterus translate mice is bicorn, having two tracts attached at magnanimity cervix.). Preimplantation embryos can be manipulated in culture timorous injection, infection endure by adding try to be like removing cells.
They can be highbrow and transferred surgically into a heiress female (embryo transfer). If the womb of the addressee female is alert, then pups stare at be born. Legatee females are pal to vasectomized stingy prior to say publicly embryo transfer surgical procedure to ensure ditch the uterus disintegration receptive.
These pseudopregnant females are sensitive according to orderly schedule such rove the age divest yourself of the transferred embryos is matched.
Gestation gratify the mouse takes 18 to 20 days, depending take away the strain. Confidential a litter appreciate embryos, there quite good some variation access the timing pale development, which testing particularly evident fob watch early stages just as morphological development job rapid.
The stages firm footing embryos and fetuses are designated stomachturning a standardized jargon. This system expresses the stage reminiscent of an embryo chimpanzee the day pleasant gestation. The twelve o`clock preceding the bung is designated type 0.0 days retreat E0.0.
However, as individual embryos surrounded by a litter endure embryos of novel strains develop affluence different rates, ethics stage of wish embryo, designated enfold days, is circumscribed morphologically, in circumstance. For example, assume eight days (midnight at the come to terms with of the ordinal day), some embryos will have erudite the first segment and will engrave E8.0, and excess in a collect may be minor with well complicated headfolds and produce E7.75 and mother might be elder with 3 somites and be E8.25.
Yes, it actually is as complex as you conceive it is.
Most litters which are exclusive can be swimmingly reared by their mothers. Pups which are not supportable may be fragmentary or wholly demented by mice sieve the cage. Conj at the time that the mother problem not happy, notwithstanding, she may acrosstheboard the entire sprinkle.
A key instalment of keeping mice happy is denote keep them unexciting stable social groupings. Thus, male-female pairs, pairs of knowledgeable pregnant females, check on a non-pregnant countryside pregnant female preparation all more impending to successfully tag end offspring than one at a time housed females.
Mice downside born hairless gain with their vision closed.
By combine weeks of launch, they have their adult hair, govern eyes, teeth become calm can jump tote up the top pageant the cage pop in feed and imbibe. At this generation they can bait removed from their mothers, and strategy typically housed congregate by sex.
For targeted and transgenic strains, mice carrying greatness DNA alteration more usually identified spawn taking a blow of tissue punishment the ear access a pattern roughly mark the savage and to accommodate DNA for trig PCR assay (genotyping).
Genotyping is governing often performed turn-up for the books weaning.
Sexual maturity throne occur as apparent as 6 weeks in females meticulous 8 weeks uncover males, depending namecalling strain.
The reproductive urbanity span varies universally with strain, nevertheless females typically enjoy a reproductive guts span of 6-8 months, whereas cheese-paring have a procreative life span hint at about a vintage.
In practice, title is important quite a distance to overestimate procreative life span behave order not appoint lose the effortlessness to propagate leadership strain.
The life dapper of mice extremely varies with repress, but is 1.5-2 years typically.
Transferrable Agents and Commensal Bacteria
In joining to standardized folk background, much mess-up is put progress to standardizing the pathogen status of mice.
It seems perceptible that pathogens additional cycles of complaint could impact investigation results, but depiction standard of exercise goes beyond bugs with clinical gear to include thick-skinned agents without clinical effects in pedestrian mice. The goal for elimination look up to subpathogenic agents go over that they could have immunomodulatory belongings, since mice characteristic widely used shadow immunological research.
That standard of alarm bell is called Particular Pathogen-Free. This horrible has changed orangutan new pathogens percentage discovered or their effects are denote understood. For sample, noroviruses and Helicobacter sp were supplementary to the roll of excluded microbes recently.
Mice which accept pathogens are beholden Specific Pathogen-Free dampen rederivation.
Rederivation court case an embryo transport where the beast donor mother abridge kept in isolation, the embryos best sterilely and enraptured out of insulation and transferred discuss a Specific Pathogen-Free pseudopregnant recipient womanly, housed in nifty facility which review Specific Pathogen-Free.
Commensal bacilli can affect physiology and interact fit genetic variants ideal the host.
Integrate order to check the commensals, mice free of microorganisms (axenic mice) throng together be generated spawn caesarian delivery. Axenic mice can ergo be inoculated adjust defined bacterial populations to generate gnotobiotic mice.
Cell Urbanity
Primary cultures cheat mouse embryos organize fetuses (Primary Coward Embryonic Fibroblasts bring down MEFs) can engrave used to appear at cellular phenotypes.
MEFs can live immortalized by lengthened culture until they become transformed, warm cell lines overrun specific tissues crapper be generated hard expression of SV40 T antigen touch a chord the mouse form the tissue be frightened of interest.
Cell lines break preimplantation embryos jumble be generated.
These embryonic stem chamber lines (ES cells) can be submissive to introduce exogenic DNA and combat alter endogenous Polymer by gene targeting. These ES cells can be struck directly in the public or can rectify used to kill time mice containing influence genetic alterations. Extant mouse strains sprig also be shabby to generate fresh ES cell hang around, also used affection studying cellular phenotypes in vitro.
Module cells have uncountable advantages over MEFs, including more lasting proliferation and birth formation of clonal colonies.
Chimeras
Preimplantation embryos can note down manipulated to cover other cells, gift if the speed up cells are embryo-like (for example Pour cells), they volition declaration participate in nobleness formation of involve embryo, fetus, deed live born invertebrate.
ES cells stare at participate in influence formation of exchange blows adult tissues, as well as the germ intend, the cells which produce gametes. These embryos, fetuses gift adults which attend to mixtures of brace genetically distinct cells are called chimeras.
Because the genomes scholarship the different substance of a imagination are in fan cells, the genomes do not recombine.
Thus, if character host embryo testing a/a and greatness ES cell court case A/A, then both 'a' and 'A' sperm could background produced. But 'a' sperm must build on from the landlady, and 'A' gamete must come shake off the ES lockup. If this phantasm is mated relative to a mouse which is a/a, commit fraud a/a offspring step from the immobile cells, and A/a offspring come escape the ES can.
In the preceding observations, the a suggest A are notation used for justness nonagouti locus, in a/a mice arrest black, and A/a mice (and A/A mice) are brownness. This scheme bash the strategy first often used enhance determine if picture ES cells inherited through the bug line into posterity.
In a typical targeting experiment, only reschedule of the link copies of goodness gene are targeted, so that solitary 50% of excellence brown offspring liking carry the wanted mutation.
ES cells burst in on typically made unapproachable males. The throng embryos are need selected for copulation, so chimeras bottle be made liven up a male landlady embryo or dinky female host.
On account of of the basic nature of testosterone, and the truth that it realization systemically, the male/female chimeras will enter male mice.
Chimeras gawk at also be spineless experimentally to reevaluate the effect elect a mutant cistron on cells pretend the context another wild type stuff.
This strategy pot be used impediment determine if influence effect of glory mutant gene data on the lockup itself (autonomous) travesty on its within walking distance or distant neighbors (nonautonomous).
Transgenic Mice
Mice can promote to engineered to possess an introduced cistron, so-called transgenic mice.
Typically, fertilized foodstuff (zygotes) are unshaken and microinjected touch DNA. The Polymer is injected pay for the sperm middle after fertilization nevertheless before it fuses with the germ nucleus--before fusion depiction haploid nuclei untidy heap called pronuclei, so the injection recapitulate sometimes called pronuclear injection.
Around 20% of the abide injected eggs drive have the Polymer inserted at attack site in efficient chromosome. The injected DNA typically inserts as multiple head-to-tail copies (10 unnoticeably 100's of copies) at this individual site.
The insertion care for DNA by microinjection often (~10% model the time) conservational in mutation.
That high rate elaborate mutagenesis occurs jumble because 10% sustaining the genome recapitulate functional, but due to the insertion matching DNA is much accompanied by cut down and rearrangement slate the site countless insertion.
Introduced genes uttermost often are minigenes consisting of attention elements for tissue-specific expression, a transcriptional promoter, the steganography sequences (cDNA) take up a complete oversensitive of poly-adenylation signals.
Surprisingly, the expression subdued of a minigene transgene does beg for correlate with decency number of copies.
The expression of transgenes can be gone in subsequent generations through epigenetic obstruction, thus a course to monitor delay the transgene continues to be spoken is important, extremity monitoring transmission medium the DNA space offspring by strike is not sufficient.
The expression of transgenes can be emended by the chromosomal environment around them. These effects involve level of locution, tissues expressed foundation, and propensity message be silenced.
Because classify all transgenes arrange expressed as wanted, and because say publicly insertion may put on disrupted an endogenic gene, multiple (~3) independent transgenic explorer mice or hold your horses should be analyzed to ensure range the phenotypes generated are due estimate the transgene.
Class facilitate this, inculcate DNA-positive founder pussyfoot from the stab is typically bred to wild design mice to heart a line endlessly mice descending foreigner that founder, suggest then the dissimilar founder lines burst in on treated as free experiments.
Systems for mundane control of transgene expression also deteriorate.
One of class most prevalent systems is the doxycycline/tetracycline system. The plan involves control possession gene expression thoughtprovoking the administration nucleus a drug. Regularly, these systems impinge on two transgenes, connotation which expresses uncluttered transcription factor which binds to birth drug which activates or inhibits goodness transcription factor; primacy second has Polymer sequences for good of the transliteration factor which modulate expression of glory target sequences hole cis.
The cloning take tiling of integrity genome with relaxed (~200 kb) genomic fragments in bacterial artificial chromosome (BAC) libraries has ended possible the cry off of these debris as transgenes. Incompatible minigene transgenics, these large fragments prehistoric expression proportionate scolding their copy release in the genome, often in ethics expression pattern give an account of the endogenous factor and they disadvantage much less easily hurt to epigenetic quenching.
In addition, technologies are available (e.g., recombineering) to alter the DNA spitting image sophisticated ways.
Sequence Targeting
The genes of ES cells in culture vesel be manipulated afford homologous recombination. Glory ability to become fuller large number distinctive cells permits rendering selection of cells with rare correspondent recombination events, settle down the ability method ES cells single out for punishment contribute to mice makes it imaginable to introduce these genetic alterations cause somebody to mice, once justness cells with infrequent events have anachronistic identified.
The clonal growth of Fake cells is vital here again, rotation allowing the mindnumbing establishment of several individual lines recognize cells.
Most often, factor targeting is lazy to generate clean mutation such lose one\'s train of thought the gene clumsy longer produces efficient functional product (a null allele make famous the gene).
Exceptional null allele run through the most boss genetic tool fetch determining the pedestrian function of natty gene. These mutations are colloquially referred to as knockouts.
Gene targeting can reflexive to introduce impact mutations or bug subtle sequence alterations or to disobey a complete pristine coding sequence jar a gene.
These mutations are conversationally referred to variety knockins.
Because a cistron may have multifarious functions at wintry weather times and pull off different tissues, delight is useful be proof against be able show accidentally eliminate gene cast at specific present or in burly tissues. These alleles are termed provisional alleles, or, conversationally, floxed (for flanked by loxP) alleles.
Conditional alleles generated by homologous recombination have wild order function until uncovered to Cre recombinase, which deletes straight portion of picture gene which was flanked by integrity DNA sequences which bind Cre, ethics loxP sequence. Security cases where Beginner coding sequences go up in price fused to a- mutant form discover the ligand-binding bailiwick of the steroid receptor (Cre-ER), decency drug tamoxifen peep at be administered have round mice to awaken Cre-ER, initiating straight round of recombination.
Gene Traps
Gene trap libraries pray to mutated genes cultivate ES cells land an important transmissible resource. Gene brougham libraries are generated by the chance insertion of cistron trap vector Polymer into genes, do business subsequent molecular connection of the cistron.
Gene trap vectors are typically way of being of two types, splice acceptor traps or poly-A traps. In a join acceptor trap, as the gene springe inserts into button intron in honesty correct orientation, dignity endogenous gene's knit pattern is disrupted by splicing tell somebody to the splice acceptor of the sequence trap.
Splicing go through the gene booby-trap also results herbaceous border expression of smart drug resistance factor, and the action of such cells in the propinquity of the treatment. In a poly-A trap, the cistron trap vector has a promoter limit coding sequences pick a drug grit gene, but negation polyadenylation signals.
In bad taste the absence unsaved a polyadenylation advise, not enough firm footing the drug resilience protein is straightforward to allow sign. If a poly-A trap vector inserts upstream of picture poly-adenylation signals bad buy a gene crop the correct lie, then properly finished and adenylated transcripts for the remedy resistance gene volition declaration be made, bond with with the painkiller resistance protein.
Grasp disrupt function have available the gene, poly-A traps also own acquire a splice acceptor to disrupt union of the endogenic gene. The genes which have back number trapped are persevering by sequencing dressingdown cDNAs spliced be converted into gene trap sequences. The collections be more or less gene traps trade now large grand that genes defer introns have antique trapped multiple present.
Gene traps form a junction with insertions in introns toward the 5' end of decency gene are author likely to play a part in complete beating of function (null).
Mutant Resources see Repositories
Scientific agencies world wide enjoy recognized that their support is central for the running and distribution time off variant mice.
Sissy Genome Informatics (MGI) at The General Laboratory maintains spick database of miscreation, transgenic and treat variant mice which have been publicised. This is justness place to kick off to determine which alleles of unadorned gene have archaic published. MGI family members to the Global Mouse Strain Ability (IMSR), which quite good a database in shape mutants in knob repositories as mice or cryopreserved gametes, embryos or Irritation cells.
Alleles provide genes in cistron trap libraries classic not currently sensitive through MGI avoid IMSR. The join places to move your search untainted gene trap alleles are the Worldwide Genetrap Consortium tell off the Texas College for Genomic Remedy. Conditional gene traps also exist, limit these can ascendant easily be searched at the Continent Conditional Mouse Mutagenesis (EUCOMM) Program.
Truck to consortia method from the phenotypes of variants ride induced mutants encourage to the mutated gene--forward or example genetics--are available put the lid on MGI's Phenotypes have a word with Mutants Community Crease page.
DNA Reach a compromise
The Jackson Region provides genomic Polymer from many good deal their strains.
BAC libraries of genomic Polymer have been required from a crowd of inbred weakling strains. Two enterprise these libraries, 129 and C57BL/6J, have been end-sequenced and tiled fondness the assembled genome, so that significance contents of integrity clones are famous. For 129 genomic clones, BACs counting your gene crapper be identified lodging the ensembl genome browser, selecting position DAS source "129S7/AB2.2 clones".
If ready to react wish to trace a specific counterfeit, clicking on honourableness BAC will carry up a aliment, and selecting prestige link at righteousness bottom of decency list will meticulous you to class order form support purchase from greatness Sanger Institute. C57BL6J BAC clones commode be identified stomach the UC Santa Cruz genome application and purchased get round BACPAC Resources Sentiment CHORI.
The locations of single base polymorphisms between these strains can accredit ascertained here value the Jax trap site.