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The importance of the p53 pathway in retinoblastoma was shown in mice with retinas lacking Rb, p107, and p53 [1]. These mice developed bilateral retinoblastoma with 100% penetrance and a short latency; thus, they are ideal for testing new chemotherapeutic drugs. Rb was conditionally inactivated in retinal progenitor cells by using the Chx10-Cre transgenic mouse line and the RbLox allele. On a p107-deficient genetic background, these mice develop retinoblastoma with a penetrance of approximately 60%. However, the disease rarely progresses to invasive retinoblastoma with ocular hypertrophy, and the mice rarely become moribund. In contrast, mice lacking both copies of p53, Rb, and p107 (Chx10-Cre;RbLox/−;p53Lox/−;p107−/−) in their retinal progenitor cells develop aggressive, invasive retinoblastoma. More importantly, penetrance is 100% as bilateral retinoblastoma with a short latency (100.3 ± 42.3 days), which is ideal for testing new chemotherapeutic drugs. Interestingly, mice with one copy of wild-type Rb also develop invasive, aggressive retinoblastoma, but with a longer latency than do Chx10-Cre;RbLox/−;p53Lox/−;p107−/− mice. Preliminary studies indicated that these tumors have lost heterozygosity at the Rb locus; thus, Chx10-Cre;RbLox/−;p53Lox/−;p107−/− mice are the only mouse model of retinoblastoma that recapitulates this feature of human retinoblastoma.

Michael A. Dyer, Carlos Rodriguez-Galindo, Matthew W. Wilson. Use of Preclinical Models to Improve Treatment of Retinoblastoma. PLoS Med. 2, 10, e332. PMID 16231976. DOI:10.1371/journal.pmed.0020332

11-12-2007

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