Biomaterial Database

A foreign dihydrofolate reductase gene in transgenic mice acts as a dominant mutation. 1986

J W Gordon

We have produced 17 lines of transgenic mice by microinjecting a full-length cDNA clone of an altered dihydrofolate reductase (dhfr) gene. The protein specified by this gene carries a point mutation which triples its Km for dihydrofolate and reduces substrate turnover 20-fold relative to the wild-type enzyme. Transgenic mice from different pedigrees, several of which carry a single copy of this gene in different integration sites, manifest an array of similar developmental abnormalities including growth stunting, reduced fertility, pigmentation changes, and skeletal defects. These defects appear in animals heterozygous for the foreign gene. RNA analyses demonstrate significant expression of the cDNA in newborn mice and adult tissues. These findings show that the additional dhfr gene exerts its mutational effects in a dominant fashion, and therefore the data indicate that transgenic mice can serve as models for elucidating mechanisms of dominant mutagenesis.

UI	MeSH Term	Description	Entries
D007247	Infertility, Female	Diminished or absent ability of a female to achieve conception.	Sterility, Female,Sterility, Postpartum,Sub-Fertility, Female,Subfertility, Female,Female Infertility,Female Sterility,Female Sub-Fertility,Female Subfertility,Postpartum Sterility,Sub Fertility, Female
D008817	Mice, Mutant Strains	Mice bearing mutant genes which are phenotypically expressed in the animals.	Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D002970	Cleavage Stage, Ovum	The earliest developmental stage of a fertilized ovum (ZYGOTE) during which there are several mitotic divisions within the ZONA PELLUCIDA. Each cleavage or segmentation yields two BLASTOMERES of about half size of the parent cell. This cleavage stage generally covers the period up to 16-cell MORULA.	Segmentation Stage, Ovum,Cleavage Stages, Ovum,Ovum Cleavage Stage,Ovum Cleavage Stages,Ovum Segmentation Stage,Ovum Segmentation Stages,Segmentation Stages, Ovum
D005260	Female		Females
D005313	Fetal Death	Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.	Fetal Mummification,Fetal Demise,Death, Fetal,Deaths, Fetal,Demise, Fetal,Fetal Deaths,Mummification, Fetal
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005799	Genes, Dominant	Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.	Conditions, Dominant Genetic,Dominant Genetic Conditions,Genetic Conditions, Dominant,Condition, Dominant Genetic,Dominant Gene,Dominant Genes,Dominant Genetic Condition,Gene, Dominant,Genetic Condition, Dominant
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia