We found that exactly under our specific experimental conditions and a C57BL/6J �� 129Sv mixed genetic background, Recql5+/+ApcMin/+ mice developed 72.9 �� 12.7 (mean �� SE) macroadenomas (diameter �� 1 mm) along the entire intestinal tract at 90 d (Figure (Figure1A1A and andC).C). Remarkably, Recql5-/-ApcMin/+ littermates developed 142.5 �� 9.4 macroadenomas at the same age, which is significantly higher than that observed in their Recql5+/+ApcMin/+ littermates (P = 0.0032) (Figure (Figure1A1A and andC,C, Table Table1).1). In particular, 15 out of 19 Recql5-/-ApcMin/+ mice (78.9%) had more than 100 macroadenomas (Figure (Figure1B1B and andC)C) compared with only 1 out of 7 (14.2%) of such individuals in the Recql5+/+ApcMin/+ cohort.

Interestingly, however, although the average number of microadenomas (diameter < 1 mm) was higher in the Recql5-/-ApcMin/+ cohort than in mice of the corresponding Recql5+/+ApcMin/+ cohort, the difference did not reach a significant level (P = 0.1048, Figure Figure1D,1D, Table Table11). Table 1 Effect of Recql5 status on the intestine polyp multiplicity (�� SE) of Apcmin/+ mice at age 90 d Figure 1 Effects of Recql5 deficiency in the development of intestinal adenomas in the ApcMin/+ mice. Recql5+/+ApcMin/+ and Recql5-/-ApcMin/+ mice were monitored and sacrificed at 90 d of age. A, B: Representative microscopic images of sections from the ileum ... Previous studies have shown that although ApcMin/+ mice are highly prone to intestinal adenomas, colonic tumors were relatively infrequent (< 50% penetrance) in these mice[16].

We found, however, that Recql5 deficiency Carfilzomib had a significant impact on the incidence of colonic tumors in these mice. It resulted in an increase of the colonic tumor incidence to 94.1% (16 out of 17 mice) (Figure (Figure2).2). Moreover, microscopic examination revealed that some Recql5+/+ApcMin/+ mice developed only small polyp-like nodules in their colons (Figure (Figure2A,2A, Table Table1),1), whereas most Recql5-/-ApcMin/+ mice had multiple macroadenomas in each colon (Figure (Figure2B,2B, Table Table1).1). Together, this data clearly indicate that Recql5 deficiency could play an important role in the development of intestinal adenomas in ApcMin/+ mice. Figure 2 Effects of Recql5 deficiency in the development of colonic adenomas in the ApcMin/+ mice. A, B: Representative images of sections from the colon of a Recql5+/+ApcMin/+ (A) and a Recql5-/-ApcMin/+ (B) mouse. Note that A and B are shown at different magnifications. … DISCUSSION Previous studies have shown that ApcMin/+ mice on a congenic C57BL/6 background develop 30 to 50 macroadenomas at 90 to 120 d of age, respectively[16]. We found that under the mixed genetic background resulting from intercrossing between B6/129.