Tert Conditional Knockout mouse models

Tert encodes the mouse ortholog of human TERT, the catalytic reverse transcriptase subunit of telomerase, which assembles with the noncoding RNA template Terc plus dyskerin, NOP10, NHP2, and GAR1 and is recruited to chromosome ends by TPP1 to add telomere repeats, using an N-terminal essential domain, an RNA binding domain, and a canonical reverse transcriptase fold. Human cancer activates TERT chiefly through recurrent promoter mutations at positions 124 and 146 upstream of the start codon, which create de novo GABP ETS binding sites and reactivate transcription in melanoma, glioblastoma, bladder cancer, and hepatocellular carcinoma, whereas germline loss-of-function alleles cause dyskeratosis congenita, aplastic anemia, and pulmonary fibrosis. A critical species caveat governs design: laboratory mice carry very long telomeres and tolerate Tert deletion for several generations, so nulls model attrition only after successive intercrossing or on a Terc-deficient background. Promoter-humanized or hTERT knockin alleles are therefore the appropriate choice for promoter mutation biology and telomerase-directed therapeutics.

A floxed Tert allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.