Abstract
This chapter brings together a variety of information and concepts that are important for understanding the following chapters. The first section is an overview concerning mouse reproductive biology and embryology. This topic is important because, nowadays, many experiments in genetics require the manipulation of embryos at different stages of development, either to study their phenotype or for the production of chimeras with other embryos or with genetically engineered embryonic stem (ES) cells. The second part is a compilation of concepts of general or molecular genetics related to the phenotypic expression of mutations. More information can also be retrieved from several websites, where books and manuals are freely available online.
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Notes
- 1.
The website http://informatics.jax.org/ is a fundamental database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data. It is a true “gold mine” for mouse geneticists to which we will frequently refer. Several books dealing with some fundamental aspects of mouse biology are freely available at this website.
- 2.
The reproductive activity of wild mice is interrupted or reduced during winter. This period is called anestrus.
- 3.
Estrus, sometimes spelled oestrus (UK), is a noun; estrous (oestrous) is the corresponding adjective.
- 4.
For some precisely timed pregnancies, female mice must sometimes be bred in a “light-reversed” environment.
- 5.
Such a vaginal plug is specific to the Mus genus and does not exist, for example, in the rat. Whether it confers a selective advantage to the species is an open question.
- 6.
As mentioned, most matings occur during the night; this is why “plugging” must be achieved preferably during the morning of the following day. Detection of a plug is sometimes very easy, especially when it bulges out of the vagina. In other instances, a probe may be necessary to detect resistance when gently inserted into the vagina. The type of probe used by ophthalmologists to unclog the tear ducts of human patients is a perfect tool for this task.
- 7.
Dating the different steps of mouse embryonic development has been a matter of controversy. Some embryologists wanted the first day of pregnancy to be designated day 1; others argued that it should be day 0. In fact, the most accurate dating takes into account that, when the vaginal plug is discovered, the embryo is at 0.5 days of development. At this time it is a one-cell embryo just after fertilization (E0.5) (based on Theiler 1972).
- 8.
Resorption of the corpora lutea is triggered by prostaglandins secreted by the placenta.
- 9.
A gentle pressure on the pelvis of the mouse allows one to detect the relaxation of the pelvic girdle.
- 10.
Making the observation of non-viable (stillbirth) phenotypes difficult.
- 11.
If this is not the case, the pups are left outside of the nest; they progressively cool, do not move much, and have no milk in their stomachs. Foster nursing is then urgent.
- 12.
Selecting a mother nursing a litter with a different coat color (albino/non-albino) is a clever way to check the success of the adoption without perturbing the mother.
- 13.
A useful and reliable criterion is the average number of mice weaned per mated female per week.
- 14.
The response to gonadotropin injections may also vary from one batch of hormone to the next.
- 15.
An ear speculum is an ideal tool. The extremity of a 20-ml glass pipette would also fit perfectly for this purpose.
- 16.
The t-haplotype is a small chromosomal region of chromosome 17 that is highly polymorphic among wild mice of the Mus m. domesticus species. Frequently, t-haplotypes of wild origin are not transmitted by heterozygous males in compliance with Mendel’s laws (i.e., 50:50), but at a much higher frequency (95:5 or even 99:1).
- 17.
It is for the rapid and safe identification of the origin of its progeny that mice of the strain 129/J segregate for the coat color alleles Tyr c and Tyr ch.
- 18.
Experiments performed at the Harwell (MRC) Research Centre have demonstrated that the damage caused by radiation (cosmic rays) to mouse embryos when stored at low temperatures for very long periods is practically negligible.
- 19.
It is not easy to observe twins by the mere examination of the implants in the mouse uterus, as placental fusion is frequent in this species.
- 20.
Discordances between the number of implants (dead or alive) and the number of corpora lutea does not support the idea that twinning commonly occurs in the mouse.
- 21.
Twinning (sometimes called “polyembryony”) is the rule in nine-banded armadillos of the South American species Dasypus novemcinctus. In this species, the females regularly deliver progenies composed of four monozygotic twins. This regular production of genetically identical offspring makes the species a valuable model for multiple births.
- 22.
Cells of the cumulus oophorus are ovarian (but somatic) cells. They surround the oocyte and are shed with it upon ovulation.
- 23.
Cells with 2n + 1 chromosomes (trisomic) are in general more viable than cells with 2n − 1 chromosomes (monosomic).
- 24.
Sometimes called tetraparental chimeras.
- 25.
This cavity is often called a blastocoel.
- 26.
G.W. Beadle and E.L. Tatum were awarded the Nobel Prize in Physiology or Medicine in 1958 for their discovery of the “role of genes in regulating biochemical events within cells”.
- 27.
The transcriptome corresponds to the full set of RNA molecules that are transcribed from the genome. This point will be extensively discussed in Chap. 5.
- 28.
The word electromorph has been coined to define the alleles characterized by a different global electrical charge.
- 29.
When an allele is fully dominant, geneticists often write the genotype Mut/–, indicating that the allele in question completely determines the phenotype.
- 30.
These yellow mice posed a problem to Cuénot while he was trying to demonstrate that Mendel’s laws also apply to mammals. When intercrossing A y/A mice, he did not find the expected 1:2:1 proportions of phenotypes for a single gene with two alleles, but instead found a 1:2:0 ratio. However, Cuénot provided the correct explanation for these “unusual” proportions.
- 31.
A mutation that leads to the synthesis of a mutant protein that interferes or disrupts the activity of the wild-type protein in the multimer is called a dominant-negative mutation. A typical example is found in the syndrome of osteogenesis imperfecta (O.I. Type III) in which structurally defective type I collagen is formed.
- 32.
Genome annotation consists of attaching biological information to a particular DNA sequence, or of establishing a link between a gene (or a small chromosomal region) and a given phenotype by any possible means.
References
Bradley A, Evans M, Kaufman MH, Robertson E (1984) Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309:255–256
Brinster RL (1974) The effect of cells transferred into the mouse blastocyst on subsequent development. J Exp Med 140:1049–1056
Bruce HM (1959) An exteroceptive block to pregnancy in the mouse. Nature 184:105
Byers SL, Wiles MV, Dunn SL, Taft RA (2012) Mouse estrous cycle identification tool and images. PLoS ONE 7:e35538
Colucci-Guyon E, Portier MM, Dunia I, Paulin D, Pournin S, Babinet C (1994) Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell 79:679–694
Condamine H, Custer RP, Mintz B (1971) Pure-strain and genetically mosaic liver tumors histochemically identified with the -glucuronidase marker in allophenic mice. Proc Natl Acad Sci USA 68:2032–2036
Danforth CH (1947) Heredity of polydactyly in the cat. J Heredity 38:107–112
De Repentigny Y, Kothary R (1996) An improved method for artificial insemination of mice–oviduct transfer of spermatozoa. Trends Genet 12:44–45
de Vries H (1910) Intracellular pangenesis (trans from German: Stuart Gager C). The Open Court Publishing Co., Chicago
Detlefsen JA (1921) A new mutation in the house mouse. Amer Nat 55:469–476
Dietrich WF, Lander ES, Smith JS, Moser AR, Gould KA, Luongo C, Borenstein N, Dove W (1993) Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell 75:631–639
Eicher EM, Hoppe PC (1973) Use of chimeras to transmit lethal genes in the mouse and to demonstrate allelism of the two X-linked male lethal genes jp and msd. J Exp Zool 183:181–184
Fox JG, Barthold SW, Davisson MT, Newcomer CE, Quimby FW, Smith AL (2007) The mouse in biomedical research, 2nd edn. Elsevier, New York
Gardner RL, Lyon MF (1971) X chromosome inactivation studied by injection of a single cell into the mouse blastocyst. Nature 231:385–386
Glenister PH, Rall WF (2000) Cryopreservation and rederivation of embryos and gametes. In: Jackson IJ, Abott CM (eds) Mouse genetics and transgenics: a practical approach. Oxford University Press, Oxford
Grüneberg H (1952) The genetics of the mouse. Martinus Nijhoff, The Hague
Guénet JL, Babinet C (1978) The hairy ear mutation (Eh) is not cell lethal. Mouse News Letter 58:67
Guénet JL, Marchal G, Milon G, Tambourin P, Wendling F (1979) Fertile dominant spotting in the house mouse. J Hered 70:9–12
Hauschka TS, Jacobs BB, Holdridge BA (1968) Recessive yellow and its interaction with belted in the mouse. J Hered 59:339–341
Hedrich HJ (2012) The laboratory mouse, 2nd edn. Elsevier Academic Press, Amsterdam
Hogan ME, King LE Jr, Sundberg JP (1995) Defects of pelage hairs in 20 mouse mutations. J Investig Dermatol 104(5 Suppl):31S–32S
Illmensee K, Kaskar K, Zavos PM (2005) Efficient blastomere biopsy for mouse embryo splitting for future applications in human assisted reproduction. Reprod Biomed Online 11:716–725
Kamimura S, Inoue K, Ogonuki N, Hirose M, Oikawa M, Yo M, Ohara O, Miyoshi H, Ogura A (2013) Mouse cloning using a drop of peripheral blood. Biol Reprod 89:24
Kang L, Wang J, Zhang Y, Kou Z, Gao S (2009) iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell 5:135–138
Kaufman MH, O’Shea KS (1978) Induction of monozygotic twinning in the mouse. Nature 276:707–708
Kobayashi T, Yamaguchi T, Hamanaka S, Kato-Itoh M, Yamazaki Y, Ibata M, Sato H, Lee YS, Usui J, Knisely AS, Hirabayashi M, Nakauchi H (2010) Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell 142:787–799
Leckie PA, Watson JG, Chaykin S (1973) An improved method for the artificial insemination of the mouse (Mus musculus). Biol Reprod 9:420–425
Luo C, Zuñiga J, Edison E, Palla S, Dong W, Parker-Thornburg J (2011) Superovulation strategies for 6 commonly used mouse strains. J Am Assoc Lab Anim Sci 50:471–478
McLaren A, Molland P, Signer E (1995) Does monozygotic twinning occur in mice? Genet Res 66:195–202
Miko I (2008) Phenotype variability: penetrance and expressivity. Nature Education 1:137
Mintz B (1962) Formation of genetically mosaic mouse embryos. Am Zool 2:432
Mintz B, Baker WW (1967) Normal mammalian muscle differentiation and gene control of isocitrate dehydrogenase synthesis. Proc Natl Acad Sci USA 58:592–598
Mintz B, Illmensee K (1975) Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci USA 72:3489–3585
Mintz B, Silvers W (1967) “Intrinsic” immunological tolerance in allophenic mice. Science 158:1484–1487
Mochida K, Hasegawa A, Taguma K, Yoshiki A, Ogura A (2011) Cryopreservation of Mouse Embryos by Ethylene Glycol-Based Vitrification. J Vis Exp 57:e3155. doi:10.3791/3155
Moser AR, Pitot HC, Dove WF (1990) A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247:322–324
Nadeau JH (2003) Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13:290–295
Nagy A, Gertsenstein M, Vintersten K, Behringer R (2003) Manipulating the mouse embryo, a laboratory manual, 3rd edn. Cold Spring Harbor Press, New York
Nakagata N (2011) Cryopreservation of mouse spermatozoa and in vitro fertilization. Methods Mol Biol 693:57–73
Nakagata N, Takeo T, Fukumoto K, Haruguchi Y, Kondo T, Takeshita Y, Nakamuta Y, Umeno T, Tsuchiyama S (2014) Rescue In Vitro Fertilization Method for Legacy Stock of Frozen Mouse Sperm. J Reprod Dev 60(2):168–171
Nishizono H, Shioda M, Takeo T, Irie T, Nakagata N (2004) Decrease of fertilizing ability of mouse spermatozoa after freezing and thawing is related to cellular injury. Biol Reprod 71:973–978
Ogonuki N, Inoue K, Hirose M, Miura I, Mochida K, Sato T, Mise N, Mekada K, Yoshiki A, Abe K, Kurihara H, Wakana S, Ogura A (2009) A high-speed congenic strategy using first-wave male germ cells. PLoS ONE 4:e4943. doi:10.1371/journal.pone.0004943
Ogonuki N, Inoue K, Ogura A (2011) Birth of normal mice following round spermatid injection without artificial oocyte activation. J Reprod Dev 57:534–538
Ogonuki N, Mochida K, Miki H, Inoue K, Fray M, Iwaki T, Moriwaki K, Obata Y, Morozumi K, Yanagimachi R, Ogura A (2006) Spermatozoa and spermatids retrieved from frozen reproductive organs or frozen whole bodies of male mice can produce normal offspring. Proc Natl Acad Sci USA 103:13098–13103
Ogura A, Ogonuki N, Inoue K, Mochida K (2003) New microinsemination techniques for laboratory animals. Theriogenology 59:87–94
Ogura A, Ogonuki N, Miki H, Inoue K (2005) Microinsemination and Nuclear Transfer Using Male Germ Cells. Int Rev Cytol 246:189–229
Olds-Clarke P (1989) Sperm from tw32/+ mice: capacitation is normal, but hyperactivation is premature and nonhyperactivated sperm are slow. Dev Biol 131:475–482
Panthier JJ, Guénet JL, Condamine H, Jacob J (1990) Evidence for mitotic recombination in W(ei)/+ heterozygous mice. Genetics 125:175–182
Papaioannou VE, McBurney MW, Gardner RL, Evans MJ (1975) Fate of teratocarcinoma cells injected into early mouse embryos. Nature 258:70–73
Perez CJ, Jaubert J, Guénet J-L, Barnhart KF, Ross-Inta CM, Quintanilla VC, Aubin I, Brandon J, Otto N, DiGiovanni J, Gimenez-Conti I, Giulivi C, Kusewitt DF, Conti CJ, Benavides F (2010) Two hypomorphic alleles of mouse Ass1 as a new animal model of citrullinemia type I, and other hyperammonemic syndromes. Am J Pathol 177:1958–1968
Silvers WK (1979) The coat colors of mice: a model for mammalian gene action and interaction. Springer, Berlin
Stewart CL, Gadi I, Bhatt H (1994) Stem cells from primordial germ cells can reenter the germ line. Dev Biol 161:626–628
Sztein J, Vasudevan K, Raber J (2010) Refinements in the cryopreservation of mouse ovaries. J Am Assoc Lab Anim Sci 49:420–422
Sztein JM, Farley JS, Mobraaten LE (2000) In vitro fertilization with cryopreserved inbred mouse sperm. Biol Reprod 63:1774–1780
Taft RA, Low BE, Byers SL, Murray SA, Kutny P, Wiles MV (2013) The perfect host: a mouse host embryo facilitating more efficient germ line transmission of genetically modified embryonic stem cells. PLoS ONE 8:e67826. doi:10.1371/journal.pone.0067826
Tarkowski A (1998) Mouse chimaeras revisited: recollections and reflections. Int J Dev Biol 42:903–908
Tarkowski AK (1961) Mouse chimaeras developed from fused eggs. Nature 190:857–860
Theiler K (1972) The house mouse. Springer, New York
Van der Lee S, Boot LM (1956) Spontaneous pseudopregnancy in mice II. Acta Physiol Pharmacol Neerl 5:213–215
Vergara GJ, Irwin MH, Moffatt RJ, Pinkert CA (1997) In vitro fertilization in mice: Strain differences in response to superovulation protocols and effect of cumulus cell removal. Theriogenology 47:1245–1252
Wakayama S, Kohda T, Obokata H, Tokoro M, Li C, Terashita Y, Mizutani E, Nguyen VT, Kishigami S, Ishino F, Wakayama T (2013) Successful serial recloning in the mouse over multiple generations. Cell Stem Cell 12:293–297
Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R (1998) Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394:369–374
West JD, Frels WI, Papaioannou VE, Karr JP, Chapman VM (1977) Development of interspecific hybrids of Mus. J Embryol Exp Morphol 41:233–243
Whitten WK (1956) Modification of the oestrous cycle of the mouse by external stimuli associated with the male. J Endocrinol 13:399–404
Whittingham DG (1968) Fertilization of mouse eggs in vitro. Nature 220:592–593
Whittingham DG, Leibo SP, Mazur P (1972) Survival of mouse embryos frozen to −196 degrees and −269 degrees C. Science 178:411–414
Wilmut I (1972) The effect of cooling rate, warming rate, cryoprotective agent and stage of development on survival of mouse embryos during freezing and thawing. Life Sci II 11:1071–1079
Wolfe HG (1967) Artificial insemination of the laboratory mouse (Mus musculus). Lab Anim Care 17:426–432
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Reference Book
Papaioannou VE, Behringer R (2005) Mouse phenotypes: a handbook of mutation analysis. CSHL Press, New York, p 235
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Guenet, JL., Benavides, F., Panthier, JJ., Montagutelli, X. (2015). Basic Concepts of Reproductive Biology and Genetics. In: Genetics of the Mouse. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44287-6_2
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