A FULL-LENGTH NOTCH1 ALLELE IS DISPENSABLE FOR TRANSFORMATION ASSOCIATED WITH A PROVIRALLY ACTIVATED TRUNCATED NOTCH1 ALLELE IN MOLONEY MULV-INFECTED MMTVD MYC TRANSGENIC MICE/

The Notch1 gene was previously found to be targetted by provirus inser tion in a high proportion of T-cell lymphomas arising in Moloney MuLV- inoculated MMTVD/myc transgenic mice, Proviral activation of Notch1 wa s associated with overexpression of truncated Notch1, deleted of the s equences coding for the extracellular domain, The high levels of trunc ated Notch1 RNA and proteins in these tumors are thought to be involve d in the oncogenic transformation, However, in addition to these trunc ated RNA and proteins, high level expression of full-length Notch1 RNA and proteins was also observed in several tumors, suggesting that the y could also contribute to the transformation process, To test this hy pothesis, me used a genetic approach and studied MMTVD/myc transgenic mice in which one of the Notch1 alleles was mutated by targeted mutage nesis (Notch(+/-) mice). Heterozygote (Notch1(+/-)) and wild-type (Not ch1(+/+)) transgenic mice were inoculated with Moloney MuLV and the fr equency of Notch1 rearrangements was compared between both groups. Not ch1 was rearranged at similar frequencies in both groups, indicating t hat the full-length Notch1 allele is dispensable in tumors harboring a n activated Notch1 allele.