Figure 4.

Histopathology Identifies Mucosal Defects and Bone Marrow Failure as the Cause of Death in Mice with Short Telomeres

(A) Photomicrographs of spleen histology in wild-type and mTR^−/− mice showing effacement of the normal white-red pulp architecture and replacement with myelo-erythropoiesis as evidenced by the presence of megakaryocytes (arrows) in the inlet at 200X.

(B) Representative photomicrograph of typhlocolitis lesion seen in mTR^−/− mice. Compared to wild-type mice (left panel), the lamina propria and submucosa is infiltrated by neutrophils in the cecum, indicating an ongoing infection (right). There was evidence of colitis in 100% of mTR^−/− mice examined (8 of 8).

(C) Micrographs from mid-intestine showing gastrointestinal mucosal defects in wt^∗ mice. Compared with wild-type mice, in which no abnormalities were ever seen (0 of 9), wt^∗ mice had evidence of villous blunting (3 of 6). In mTR^+/− and mTR^−/− mice with short telomeres, more-severe defects were noted, including severe villar blunting adjacent to areas of crypt hyperplasia, as well as regions of complete villous atrophy and crypt loss, which were present in all mTR^−/− mice examined, as illustrated.