Progressive adverse effects on the reproductive and hematopoietic systems and progressive telomere shortening are observed in successive generations of breeding of mice that are homozygous null for the Terc gene . Germ cells exhibit decreased rates in proliferation and increased rates of apoptosis resulting in a general state of germ cell depletion; fertility is significantly diminished. Proliferative capacity of hematopoietic cells derived from bone marrow and spleen is significantly compromised.
Dr. Carol Greider, Johns Hopkins Univ School of Medicine
Early generation mice that are homozygous null for the Terc gene are phenotypically normal. No Terc transcript or telomerase activity is detected. If null mice are maintained as homozygotes, progressive adverse effects on the reproductive and hematopoietic systems are observed. By the fifth generation of homozygous intercrossing, fertility is significantly diminished. Testes size and weight is reduced by ~80%. Germ cells exhibit decreased rates in proliferation and increased rates of apoptosis resulting in a general state of germ cell depletion. Females exhibit smaller ovaries and diminished uterine horns. The proliferative capacity of hematopoietic cells derived from bone marrow and spleen is significantly compromised. Progressive generations of interbreeding the null mice results in progressive telomere shortening (4.8 +/- 2.4 kb per generation). Cells from the fourth generation onward possess chromosome ends lacking detectable telomere repeats, aneuploidy, and chromosomal abnormalities, including end-to-end fusions.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these DBA/2J-congenic mice could vary from that originally described on a B6J genetic background. We may modify the strain description if necessary as published results become available.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the entire Terc gene. The construct was electroporated into WW6 embryonic stem (ES) cells. WW6 ES cells are derived from a mixed genetic background (C57BL/6J ,129/Sv and SJL). Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice. This strain was backcrossed to C57BL/6J (Stock No. 000664) for at least seven generations. These mice arrived at The Jackson Laboratory Repository as Stock No. 004132. Some mice were bred to DBA/2J inbred mice (Stock No. 000671) for many generations using a marker-assisted, speed congenic approach to generate this DBA/2J-congenic strain (Stock No. 022527).
|Allele Name||targeted mutation 1, Ronald DePinho|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Terctm1Rdp; targeted mutation 1, Ronald DePinho|
|Gene Symbol and Name||Terc, telomerase RNA component|
|Gene Synonym(s)||mTER; mTR|
|Strain of Origin||STOCK 129/Sv and C57BL/6J and SJL|
|Molecular Note||Replacement of the entire gene with a neomycin cassette.|
|Mutations Made By|| |
Dr. Carol Greider, Johns Hopkins Univ School of Medicine
Mutant mice were bred to DBA/2J inbred mice (Stock No. 000671) for several generations using a marker-assisted, speed congenic approach to establish this congenic strain. When maintaining the live congenic colony, heterozygous mice are bred together. The coat color expected from breeding is black.
When using the mTR- mouse strain in a publication, please cite the originating article(s) and include JAX stock #022527 in your Materials and Methods section.
|Heterozygous or wildtype for Terc<tm1Rdp>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
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