Mouse Genome Informatics
cn
    Rb1tm3Tyj/Rb1tm3Tyj
Rbl2tm2.1Tyj/Rbl2tm2.1Tyj
Tg(Pax6-cre,GFP)2Pgr/0

involves: 129X1/SvJ * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• mice are moribund by 183 +/- 39 days

tumorigenesis
• visible bilateral retinoblastoma develop with rapid and consistent kinetics appearing on average at 128 +/- 18 days
• amacrine cells, a subset of progenitor cells, and Muller cells are present in tumors
• at P31 (4 animals) and P60 (3 animals) large tumors are present and all mice have retinoblastomas in each eye that seed the vitreous and anterior chamber by 4 months of age
• by 183 +/- 39 days mice have grossly distended eyes where the tumor has filled the anterior chambers and often invaded of local tissues
• tumors infiltrate the optic nerve and metastases are found in the cervical lymph nodes (11 of 28) and brain (7 of 27)

vision/eye
• at P12, apoptosis is increased and at P21 retinas contain apoptotic bodies
• the increase in apoptosis is greater than in mutant mice wild-type for Rbl2
• at P12 in the retinal periphery proliferation and apoptosis are increased and proliferation remains elevated at P21,especially in the extreme periphery
• proliferation is increased and prolonged relative to mutant mice wild-type for Rbl2
• at P21 retinas are very hypocellular, contain apoptotic bodies and many cells with large and/or irregular-shaped nuclei, and 9 of 12 have early dysplatic lesions containing Homer-Wright rosettes in the extreme periphery
• at P21, the amacrine layer is significantly reduced away from tumor areas
• increase in horizontal cells in contrast to the general hypocellularity of the retina
• rod bipolar cells are very rare or absent from retinas and retinoblastomas
• at P21, the three nuclear layers can not be distinguished, except in the central retina where Cre expression is reduced
• Tuji-positive retinal ganglion cells are very rare or completely absent from retinas and tumors
• a cone subset (positive for M-opsin) is very rare or absent from retinas and retinoblastomas
• despite the increase in proliferation retinas are very hypoplastic at P21

nervous system
• Tuji-positive retinal ganglion cells are very rare or completely absent from retinas and tumors
• a cone subset (positive for M-opsin) is very rare or absent from retinas and retinoblastomas
• at P21, the amacrine layer is significantly reduced away from tumor areas
• increase in horizontal cells in contrast to the general hypocellularity of the retina
• rod bipolar cells are very rare or absent from retinas and retinoblastomas

cellular
• at P12, apoptosis is increased and at P21 retinas contain apoptotic bodies
• the increase in apoptosis is greater than in mutant mice wild-type for Rbl2

Mouse Models of Human Disease
OMIM IDRef(s)
Retinoblastoma; RB1 180200 J:119919