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.Heterozygotes are viable, fertile, and breed well. &nbsp;Homozygous males and females produced after 5 generations of homozygous intercrosses (F5+) are reported to demonstrate significantly diminished fertility, with median survival declining over successive generations.

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.

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