D2.Cg-Terc^tm1Rdp/J

Stock number: 022527
Product name: mTR^-
Research areas: Cancer Research, Cell Biology Research, Research Tools

Description

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.

Detailed description

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.

Development

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

Symbol: Terc^tm1Rdp
Name: targeted mutation 1, Ronald DePinho
MGI accession ID: MGI:1857930
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Terc
Marker name: telomerase RNA component
Chromosome: 3
Strain of origin: STOCK 129/Sv and C57BL/6J and SJL
Molecular note: Replacement of the entire gene with a neomycin cassette.