These Mre11ATLD1/ATLD1 mice contain an A to T point mutation at nucleotide 1894, corresponding to human codon 633, of the meiotic recombination 11 homolog A (Mre11) gene. MRE11 is a component of a trimeric protein complex also containing Nbs1 and Rad50 which is involved in DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. This mutation introduces a premature stop codon, resulting in the truncation of 75 amino acids which produces a hypomorphic protein. This mutation is commonly found in human ataxia-telangiectasia like disorder (A-TLD) and Nijmegen Breakage Syndrome (NBS). A-TLD is characterized by defects in movement, coordination, and immune responses due to chromosomal instability. NBS is characterized by short stature, microcephaly, distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, and intellectual disability. Homozygous Mre11ATLD1/ATLD1 females have severely reduced fertility, with decreased embryonic viability due to genome instability and cell cycle checkpoint defects. Homozygous males are viable and fertile. These mice, and cells derived from these mice, exhibit DNA double strand break repair defects, cell-cycle checkpoint defects, and chromosomal instability. These mice are not prone to malignancy including lymphomagenesis.
