History of the use of the Mouse Embryo Model
Introduction
The mouse has contributed to an important part of research and findings in the biomedical field since the middle of the sixteenth century (Hendrich et al. 2004). In particular, the research of the mouse embryo has continued into and multiplied within the 20th century.
It's popularity over time in mammalian biology, biomedicine, immunology, oncology, pathology, and genetics is a result of:
- The efficient mouse breeding system: Which consistently monitors the characterisitcs, that are precisley known, generation after generation, thereby producing highly standardised strains (Hedrich et al. 2004).
- The metabolic and internal anatomical similarities between the mouse and the human allows for comparisons. Because of these similarities, they share similar diseases, for example, cancer, diabetes, autoimmunity, endocrine disease, and neurological dysfunctions (Hedrich et al. 2004).
- The ability to manipulate and 'shut-down' genes from the Mouse genome(???).
Please note that the following findings are based on research which have utilised the model of the mouse embryo.
Gregor Johann Mendel (1822-1884), Augustinian priest and scientist
In his notes One Hundred Years of Mouse Genetics: An Intellectual History II The Molecular Revolution (1981–2002), Kenneth Paigen wrote that Mendel's first experiment on the transmission of inheritance was made using mice. Due to complaints from members of the Catholic Church about the smell , he changed his material to Pea plants (Berry 1987).
1895: Robert Heinrich Johannes Sobotta (1869-1945), German Anatomist [1]
Researched the fertilisation and cleavage of the mouse's egg (Sobotta, 1895). Link to Dr. Sobotta's research [2]
What did he find?
- The corpus Luteum is formed by the enlargement of the epithelial cells of the follicle, aided by growth of connective tissue.*There is no distinction between corpora lutea vera and corpora lutea spuria.
- The corpora lutea do not degenerate. They remain unchanged during the life of the animal, and therefore add to the size of the ovary.
1949: John H. Hammond, Jr. (1888-1965), Animal Husbandry Scientist
"First report of attempts to culture mouse embryos in vitro to the Blastocyst stage..." (???)
What did he do?
Cultured eight-cell morulae and four-cell-stage embryos to the Blastocyst sage.
Embryos removed at the two-cell stage soon after died. (???)
1956: Wesley Kingston Whitten (1918-), Australian Veterinary Scientist
What did he do?
Cultured 8-cell mouse embryos to the Blastocyst stage.
How did he do this?
Used a medium containing Krebs-Ringer's bicarbonate solution supplemented with glucose and bovine serum albumin (???).
Soon after, he found that some two-cell-stage embryos developed into blastocysts, upon some modifications to the original medium.
He moved to the United States soon after, continuing his work in the well known, The Jackson Laboratory.
1958: Professor Dame Anne Laura Dorinthea McLaren (1927-2007), Developmental Biologist
Developed the first birth of mice in-vitro. Link to Published article [3]
1962: George Todaro (1937-) and Howard Green
- By studying the fibroblast cells of the mouse embryo , they explained how cells behave in a similar fashion once they have undergone transformation (Bhamrah et al. 2002).
How did they do this?
- Todaro and Green cultured the fibroblast cells from the mouse embryo.
What did they find?
- A few weeks after the culture, the growth rate of the Fibroblast cells slowed down. They thought that the cells, as with normal human fibroblast cells, would eventually stop didviding and die. However this was not the case.
- Two to three months later, the cell growth rate increased. This meant that the resulting new population of cells had undergone spontaneous transformation. The resulting permanently dividing cell line, called the '3T3 cell line', have been growing in culture for over 20 years. (Bhamrah et al. 2002)
1963: Ralph L. Brinster (1932-)[4], American Geneticist
What did he do?
- Determined the nutritional requirements of the pre-implantation mouse embryo.
- Established the microdrop technique that allowed two-cell-stage mouse embryos to be cultured to the Blastocyst stage (???).
1965: Beatrice Mintz (1921-)[5], American Embryologist
What did she do?
- Found that the zona pelucida of the mouse embryo could be digested using pronase (???).
- Generated adult chimeras. Link to description of a chimera [6]
1977: R.J. Mullen
What did he do?
Fused the normal and reeler mouse embryo at the morula stage to produce allophenic mice. ('The reeler mouse as a model of brain development')
1980: Ralph L. Brinster
What did he do?
The first to inject purified globin mRNA into mouse zygotes (???).
This formed the basis for the production of transgenic mice.
1983: Davor Solter (1939-), Developmental Biologist
What did he do?
Transferred nuclei between zygotes.
The importance?
Revealed the importance of parent gene imprinting in mammalian development (???).
1996: Toshio Ohshima, Jerrold M. Wardt, Chang-Goo Huht, Glenn Longenecker, Veeranna, Harish C.Pant, Roscoe O. Bradyt, Lee J. Martins, and Ashok B. Kulkarni
Generated Cyclin-dependant kinase 5 (Cdk5) null mice (a type of mutant mice) by homologous recombination to assess the role of Cdk5 in vivo. Targeted ES cells were injected into blastocysts to generate chimeric mice.
1998: Teruhiko Wakayama and Ryuzo Yanagimachi
What did they do?
Cloned the first mouse, named Cumulina.
1998: Nikola Skreb and colleagues
What did they do?
Showed that the early embryonic ectoderm contains cells capable of contributing to all three germ layers of the mouse fetus.
Use of teratocarcinomas
What are teratocarcinomas?
They are '...gonadal tumors that contain a...mixture of different tissue types, all derived from a population of undifferentiated stem cells known as embryonal carcinoma cells.' (???The white booklet)
It complemented the studies on pluripotentiality of cells from the normal embryo and allows further study of early embryonic development.
First pioneered by Leroy Stevens (Jackson Laboratory), and Barry Pierce (University of Colorado)
Leroy C. Stevens, Jr.:
- The first to identify that male mice of the inbred 129 strain have a low incidence of testicular teratoma arising from primordial germ cells (Link to Stevens and C. C. Little's related article [7] PMID: 16578442).
- The first to identify modifier genes such as ter that increase the frequency of teratomas in the testis and eventually developed an inbred strain (129/Sv).
- Developed the LT strain, in which about 50% of females develop ovarian teratocarcinomas.
Ralph Brinster(1974)[8] PMID: 4610074 , Mintz and Illmensee (1975)[9] PMID: 1059147, and Papaioannou et al. (1975) [10] PMCID: PMC433040 demonstrated that embryonic carcinoma (EC) stem cells could be injected into blastocysts to create adult chimeras that contained normal tissues derived from the EC cells.
References
1. Hedrich H., Bullock G., & Petrusz P. (2004). The Laboratory Mouse. London: Elsevier Academic Press.
2. Nagy A., Gertsenstein M., Vintersten K., & Behringer R. ( 2003). Manipulating the Mouse Embryo: A Laboratory Manual. 3rd ed. New York: Cold Spring Harbor Laboratory Press.
3. Bhamrah H.S., & Juneja K. (2002). Molecular Cell Biology. 1st ed. New Delhi: Anmol Publications.
