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.
