Roy John Britten studied DNA sequences in the US in the second half of the twentieth century, and he helped discover repetitive elements in DNA sequences. Additionally, Britten helped propose models and concepts of gene regulatory networks. Britten studied the organization of repetitive elements and, analyzing data from the Human Genome Project, he found that the repetitive elements in DNA segments do not code for proteins, enzymes, or cellular parts. Britten hypothesized that repetitive elements helped cause cells to differentiate into more specific cell kinds among different organisms.
In the early 2000s, Manjong Han, Xiaodang Yang, Jennifer Farrington, and Ken Muneoka investigated how genes and proteins in fetal mice (Mus musculus) influenced those fetal mice to regenerate severed toes at Tulane University in New Orleans, Louisiana. The group used hind limbs from mice to show how the gene Msx1 (Homeobox 7) functions in regenerating amputated digits. The researchers showed that in the process of regenerating digit tips, Msx1 genes make products that regulate or influence other genes, such as the Bone Morphogenetic Protein 4 gene (BMP4 gene), to produce proteins, such as the BMP4 proteins. The researchers also showed that BMP4 proteins, which are produced from the BMP4 gene, function in tissues during the process of limb development. Furthermore, while Msx1 genes regulate other genes during the process of regeneration, they don't produce proteins otherwise needed to organize cells in the regeneration of digit tissues. The group published their results in 2003 as Digit Regeneration Is Regulated by Msx1 and BMP4 in Fetal Mice.
Karl Oskar Illmensee studied the cloning and reproduction of fruit flies, mice, and humans in the US and Europe during the twentieth and twenty-first centuries. Illmensee used nuclear transfer techniques (cloning) to create early mouse embryos from adult mouse cells, a technique biologists used in later decades to help explain how embryonic cells function during development. In the early 1980s, Illmensee faced accusations of fraud when others were unable to replicate the results of his experiments with cloned mouse embryos. Illmensee also worked with human embryos, investigating how embryos split to form identical twins.
"A Diffusible Agent of Mouse Sarcoma, Producing Hyperplasia of Sympathetic Ganglia and Hyperneurotization of Viscera in the Chick Embryo," by Rita Levi-Montalcini and Viktor Hamburger, appeared in 1953 in the Journal of Experimental Zoology. The paper provided the first evidence that nerve growth factor is a diffusible substance. Nerve growth promoting tumors were implanted into developing embryos to determine whether the tumors stimulated growth by direct contact or by a diffusible substance. The tumors were implanted into different parts of the embryo; one set of experiments implanted the tumor directly in the embryo, while another set of experiments placed the tumor on an exterior membrane. The membrane provided a barrier to direct contact with the nervous system, and allowed some chemical interaction between the tumor and the embryo. The tumor stimulated growth in both orientations, demonstrating that nerve growth factor was a chemical agent. The paper ends with two possible conclusions for the mechanism of nerve growth, the tumor may have been directly stimulating the ganglia by a diffusible signal, or it may have reduced the resistance of the chick tissues to the nerve growth. The term "nerve growth factor" is not explicitly used in this paper, and is referred to as a "diffusible agent" or a "growth promoting agent."
As mice embryos develop, they undergo a stage of development called gastrulation. The hallmark of vertebrate gastrulation is the reorganization of the inner cell mass (ICM) into the three germ layers: ectoderm, mesoderm, and endoderm. Mammalian embryogenesis occurs within organisms; therefore, gastrulation was originally described in species with easily observable embryos. For example, the African clawed frog (Xenopus laevis) is the most widely used organism to study gastrulation because the large embryos develop inside a translucent membrane. Domestic chicken (Gallus gallus) gastrulation was also an early model organism because researchers could open the egg during development to look inside. Despite the challenges associated with studying mammalian gastrulation, the common house mouse (Mus musculus) has helped to shed light on the unique adaptations associated with mammalian development, and on the subtle differences in structure that give rise to significant divergence in late embryogenesis.
Beatrice Mintz is a brilliant researcher who has developed techniques essential for many aspects of research on mouse development. She produced the first successful mouse chimeras and meticulously characterized their traits. She has worked with various cancers and produced viable mice from the cells of a teratoma. Mintz participated in the development of transgenic mice by the incorporation of foreign DNA into a mouse genome. Her techniques have been widely applied to other studies of mouse development and are so common that many of the publications that utilize her techniques no longer remember to cite the source.
In November 2007, Masato Nakagawa, along with a number of other researchers including Kazutoshi Takahashi, Keisuke Okita, and Shinya Yamanaka, published "Generation of Induced Pluripotent Stem Cells without Myc from Mouse and Human Fibroblasts" (abbreviated "Generation") in Nature. In "Generation," the authors point to dedifferentiation of somatic cells as an avenue for generating pluripotent stem cells useful for treating specific patients and diseases. They provide background to their research by observing that previous attempts to reprogram somatic cells to a state of greater differentiability with retroviral factors Oct3/4, Sox2, c-Myc, and Klf4 had succeeded in producing induced pluripotent stem (iPS) cells that contributed to viable adult chimeras and possessed germline competency. However, as they note, the c-Myc retrovirus contributes to tumors in generated chimeras, rendering iPS cells produced with c-Myc useless for clinical applications. The authors attempt to overcome this problem by modifying the standard protocol for producing iPS cells in mice in such a way that the c-Myc retrovirus is removed. They identify problems and benefits associated with this method, but most importantly note that their method generated iPS cells that did not cause tumors in chimeric mice. Nakagawa and colleagues also report that they successfully reprogrammed adult dermal fibroblasts to return to a pluripotent state without c-Myc.
Anne Laura Dorinthea McLaren was a developmental biologist known for her work with embryology in the twentieth century. McLaren was the first researcher to grow mouse embryos outside of the womb. She experimented by culturing mouse eggs and successfully developing them into embryos, leading to advancements with in vitro fertilization.
The paper "Formation of Genetically Mosaic Mouse Embryos and Early Development of Lethal (t12/t12)-Normal Mosaics," by Beatrice Mintz, describes a technique to fuse two mouse embryos into a single embryo. This work was published in the Journal of Experimental Zoology in 1964. When two embryos are correctly joined before the 32-cell stage, the embryo will develop normally and exhibit a mosaic pattern of cells as an adult. Mosaics were easily characterized by mouse fusions from embryos of different colors; this produced clearly visible color patterns identifying the alternate cell types. Mintz referred to the fused mice as mosaic or later as allophenic, but they are more commonly known today as chimeras.
The Roscoe B. Jackson Laboratory, known commonly in the scientific field as the Jackson Laboratory, was founded by Clarence Cook Little in May 1929. The lab has been pivotal in research with in vitro fertilization, teratomas, gene replacement therapy for birth defects, and more because its researchers have focused from the beginning on developing the mouse as a model organism. Mice were chosen by researchers at Jackson as the best available model for genetic research, and today genetically uniform strains of mice developed at the lab are used in laboratories all over the world. Located at Bar Harbor on Mount Desert Island in Maine, the Jackson Laboratory focuses today on cancer research using mouse genomics.