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Publication : Off-target activity of the 8 kb Dmp1-Cre results in the deletion of Tsc1 gene in mouse intestinal mesenchyme.

First Author  Ghassib I Year  2023
Journal  Transgenic Res Volume  32
Issue  1-2 Pages  135-141
PubMed ID  36547785 Mgi Jnum  J:340850
Mgi Id  MGI:7525835 Doi  10.1007/s11248-022-00332-8
Citation  Ghassib I, et al. (2023) Off-target activity of the 8 kb Dmp1-Cre results in the deletion of Tsc1 gene in mouse intestinal mesenchyme. Transgenic Res 32(1-2):135-141
abstractText  The Dmp1-Cre mouse, expressing Cre from an 8-kb DNA fragment of the mouse Dmp1 gene, is a common tool to study gene functions in osteocytes. Here we report that the deletion of Tsc1 (TSC complex subunit 1) by 8 kb Dmp1-Cre causes rectal prolapse in mice. Histological examination shows the presence of colon polyps in Tsc1-deficient mice in association with significantly larger colon and narrower lumen, which recapitulates the common polyps pathology in Tuberous Sclerosis, an autosomal dominant disorder caused by mutations in either TSC1 or TSC2. The intestine in Tsc1-deficient mice is also enlarged with the presence of taller villi. Using the Ai14 reporter mice that express a red fluorescence protein upon Cre recombination, we show that 8 kb Dmp1-Cre activity is evident in portion of the mesenchyme of the colon and small intestine. Lastly, our data show that Tsc1 deletion by Dmp1-Cre leads to an increased proliferation in the mesenchyme of colon, which at least partly contributes to the polyps pathology seen in this mouse model and is likely a contributing factor of the polyps in Tuberous Sclerosis.
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