The first knockout mouse model of retinoblastoma

Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification

“…Mutation of Rb coupled with the absence of either p107 or p130 in chimeric or in retina-specific knockout models causes retinoblastoma (Robanus-Maandag et al, 1998;Chen et al, 2004;Dannenberg et al, 2004;MacPherson et al, 2004;Zhang et al, 2004b). These results may suggest that retinoblastoma development results from an overall reduction in 'Rb family' tumor suppressor function, which can occur equivalently through loss of pRB plus either of the Rb-related proteins.…”

“…The consistent and rapid tumorigenesis observed in the Rb/p130 DKO model makes it particularly well suited for preclinical testing of anticancer agents and chemoprevention studies. Importantly, unlike several other models of retinoblastoma, this model does not rely on mutation or inactivation of p53 (Windle et al, 1990;Howes et al, 1994;Zhang et al, 2004b;Dyer et al, 2005). In fact, p53 loss is rarely observed in human retinoblastomas (Gallie et al, 1999) although there is recent evidence that an upstream regulator of p53, MDMX, is amplified in human retinoblastomas (Laurie et al, 2006).…”

The Biology of Retinoblastoma

“…Using Chx10-Cre;Rb Lox/Lox ;p107 À/À mice, the first knockout mouse model of retinoblastoma was created by inactivating the RB1 gene in the retinal progenitor cells of p107 À/À mice. 23 Several other models using other Cre transgenic lines have since been developed. The notable difference between humans and mice is the expression of p107, since there is no compensatory increase in p107 following RB1 gene inactivation in the human retina.…”

Retinoblastoma

“…La mise au point ré cente de nouveaux modè les animaux de ré tinoblastome pourrait permettre de mieux comprendre les mé canismes biologiques et de dé velopper de nouvelles straté gies thé rapeutiques [47,15,27]. Le dé veloppement de thé rapeutique non mutagè ne comme la photothé rapie dynamique semble ê tre inté ressant en particulier chez les patients porteurs de mutation constitutionnelle de RB1 et donc à risque de second cancer [34].…”

“…RB1 a un rô le de régulation du cycle cellulaire (transition phase G1-S). Zhang et al ont montré à partir de modè les animaux transgé niques que pRB joue é galement un rô le dans la diffé renciation des cellules ré tiniennes [47].…”