All Phenotypes Rbl2<tm2.1Tyj> MGI Mouse

Mouse Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma	DOID:684	OMIM:114550	J:177573

premature death ( J:119919 )

• mice are moribund by 183 +/- 39 days

increased retinoblastoma incidence ( J:119919 )

• 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)

increased retina apoptosis ( J:119919 )

• 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

abnormal retina morphology ( J:119919 )

• 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

increased retinoblastoma incidence ( J:119919 )

• 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)

abnormal amacrine cell morphology ( J:119919 )

• at P21, the amacrine layer is significantly reduced away from tumor areas

absent retina bipolar cells ( J:119919 )

• rod bipolar cells are very rare or absent from retinas and retinoblastomas

abnormal retina horizontal cell morphology ( J:119919 )

• increase in horizontal cells in contrast to the general hypocellularity of the retina

abnormal retina neuronal layer morphology ( J:119919 )

• at P21, the three nuclear layers can not be distinguished, except in the central retina where Cre expression is reduced

absent retina ganglion cell ( J:119919 )

• Tuji-positive retinal ganglion cells are very rare or completely absent from retinas and tumors

decreased retina cone cell number ( J:119919 )

• a cone subset (positive for M-opsin) is very rare or absent from retinas and retinoblastomas

retina hypoplasia ( J:119919 )

• despite the increase in proliferation retinas are very hypoplastic at P21