Phenotypes associated with this allele

• Allele Symbol: Crb1^tm1Wij
• Allele Name: targeted mutation 1, Jan Wijnholds
• Allele ID: MGI:3052072
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Crb1^tm1Wij/Crb1^tm1Wij	involves: 129P2/OlaHsd * C57BL/6	MGI:3052122
ht2	Crb1^tm1Wij/Crb1^tm2Wij	involves: 129P2/OlaHsd * C57BL/6	MGI:3697463
cn3	Crb1^tm1Wij/Crb1^tm1Wij Crb2^tm1.1Wij/Crb2^tm1.1Wij Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JOlaHsd * SJL	MGI:5582824
cn4	Crb1^tm1Wij/Crb1^+ Crb2^tm1.1Wij/Crb2^tm1.1Wij Tg(Chx10-EGFP/cre,-ALPP)2Clc/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JOlaHsd * SJL	MGI:5582926

Genotype
MGI:3052122

hm1

• Allelic Composition: Crb1^tm1Wij/Crb1^tm1Wij
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

photosensitivity ( J:92068 )

• light exposure accelerates focal retinal degeneration

vision/eye

photosensitivity ( J:92068 )

• light exposure accelerates focal retinal degeneration

abnormal Muller cell morphology ( J:92068 )

abnormal retina photoreceptor morphology ( J:92068 )

• photoreceptor cells form half rosettes and double layers that rupture outer membrane layer and protrude into interphotoreceptor space

retina degeneration ( J:92068 )

• small regions of degeneration observable by 3 months, overall retinal function not impaired up to 9 months

nervous system

abnormal Muller cell morphology ( J:92068 )

abnormal retina photoreceptor morphology ( J:92068 )

• photoreceptor cells form half rosettes and double layers that rupture outer membrane layer and protrude into interphotoreceptor space

Genotype
MGI:3697463

ht2

• Allelic Composition: Crb1^tm1Wij/Crb1^tm2Wij
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

vision/eye

abnormal retina morphology ( J:117415 )

• at 18 months of age autofluorescent dots are seen in 5 of 6 mice but not in any control mice

• however, no abnormalities in electroretinograms are detected at 3, 8, 12,18, or 30 months of age

abnormal retina inner nuclear layer morphology ( J:117415 )

• in mice older than 8 months of age dark stained nuclei are detected in the apical part of the inner nuclear layer in areas where the outer nuclear layer is folded

abnormal retina outer nuclear layer morphology ( J:117415 )

• in some mice older than 8 months of age areas of the outer nuclear layer are folded

• mild light exposure (3000 lux for 72 h) increases the incidence of mice with folds at 8 and 12 months of age, but not at 3 months of age

thin retina outer nuclear layer ( J:117415 )

• at 18 and 24 months of age the outer nuclear layer is significantly thinner compared to controls

abnormal retina photoreceptor layer morphology ( J:117415 )

retina fold ( J:117415 )

• in some mice older than 8 months of age areas of the outer nuclear layer are folded

• mild light exposure (3000 lux for 72 h) increases the incidence of mice with folds at 8 and 12 months of age, but not at 3 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinitis pigmentosa 12		DOID:0110358	OMIM:600105	J:117415

Genotype
MGI:5582824

cn3

• Allelic Composition: Crb1^tm1Wij/Crb1^tm1Wij; Crb2^tm1.1Wij/Crb2^tm1.1Wij; Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JOlaHsd * SJL

vision/eye

abnormal retina morphology ( J:207895 )

• between E15.5 and E17.5, the adherens junctions are gradually lost in the neural retina

abnormal Muller cell morphology ( J:207895 )

• increase in the number of Sox9-positive Muller cells

increased amacrine cell number ( J:207895 )

• increase in the number of GABAergic amacrine cells and late born GlyT1 positive amacrine cells

abnormal retina bipolar cell morphology ( J:207895 )

• increase in the number of Chx10-positive bipolar cells

abnormal retina progenitor cell morphology ( J:207895 )

• increase in population of late progenitor cells and late born cells due to dysregulation of the cell cycle at E17.5

• between E15.5 and E17.5, the nuclei of the retinal progenitors show abnormal orientation

abnormal retina layer morphology ( J:207895 )

• aberrant layering in the retina is seen at 1 month of age, with a single inner plexiform layer, an abnormal thick ganglion cell layer and a second broad nuclear layer

• all retinal cell types are generated but a separate photoreceptor nuclear layer, inner and outer segment layer and outer plexiform layer are not formed

• cellular mislocalization of late born cells (rod photoreceptors, Muller cells, and bipolar cells) near the retinal pigment epithelium are seen at E13.5

abnormal retina photoreceptor layer morphology ( J:207895 )

• no distinct photoreceptor layer is formed at P5

increased retina rod cell number ( J:207895 )

• increase in the number of rods at P10

disorganized retina layers ( J:207895 )

• severe disorganization of the retina

abnormal retina outer limiting membrane morphology ( J:207895 )

• the outer limiting membrane is perturbed at E13.5

decreased total retina thickness ( J:207895 )

• retinal vasculature defects leading to the thinning of the retinas at 3-6 months of age

increased total retina thickness ( J:207895 )

• increase in retina thickness at P10 and P14 due to excessive proliferation of late-born retinal progenitor cells

retina degeneration ( J:207895 )

• retinas degenerate rapidly after 1 month

abnormal eye physiology ( J:207895 )

• from E15.5 onwards, the number of M-phase cells is increased in retinas

• proportion of retinal cells in G1 is reduced and proportion of cells in S and G2/M is increased at E17.5, however at P1 and P5, cells return to normal cell cycle

increased retina apoptosis ( J:207895 )

• increase in the number of apoptotic cells in the retinas at P10 and P14 (rod photoreceptors), and 3 months (bipolar cells)

• the number of apoptotic cells in the retina is increased at E13.5 and E17.5 onwards

abnormal electroretinogram waveform feature ( J:207895 )

• mice exhibit a greater reduction in amplitudes of electroretinogram responses at 1 month of age than single Crb2 conditional mutants, with both scotopic and photopic responses

• electroretinogram responses are below detection at 3 and 6 months of age

cellular

increased retina apoptosis ( J:207895 )

• increase in the number of apoptotic cells in the retinas at P10 and P14 (rod photoreceptors), and 3 months (bipolar cells)

• the number of apoptotic cells in the retina is increased at E13.5 and E17.5 onwards

nervous system

abnormal Muller cell morphology ( J:207895 )

• increase in the number of Sox9-positive Muller cells

increased amacrine cell number ( J:207895 )

• increase in the number of GABAergic amacrine cells and late born GlyT1 positive amacrine cells

increased retina rod cell number ( J:207895 )

• increase in the number of rods at P10

abnormal retina bipolar cell morphology ( J:207895 )

• increase in the number of Chx10-positive bipolar cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Leber congenital amaurosis 8		DOID:0110079	OMIM:613835	J:207895

Genotype
MGI:5582926

cn4

• Allelic Composition: Crb1^tm1Wij/Crb1⁺; Crb2^tm1.1Wij/Crb2^tm1.1Wij; Tg(Chx10-EGFP/cre,-ALPP)2Clc/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JOlaHsd * SJL

cellular

decreased retina apoptosis ( J:207895 )

• at P5, there is a decrease in the number of apoptotic cells in the retina

increased retina apoptosis ( J:207895 )

• the number of apoptotic cells is increased in the retina at E17.5

• however, at P5, there is a decrease in the number of apoptotic cells

vision/eye

abnormal retina morphology ( J:207895 )

• many spots and patchy areas are visible throughout the retina (pseudo-rosettes)

abnormal retina development ( J:207895 )

• disruption of the apical adherens junctions/subapical region in retinas at E15.5 which leads to ectopic localization of some photoreceptor and bipolar cells in the ganglion cell layer and ganglion, amacrine, and bipolar cells in the outer nuclear layer

abnormal retina layer morphology ( J:207895 )

• ganglion cell nuclei and inner nuclear layer cells are seen in the outer nuclear layer and some photoreceptor nuclei are seen in the ganglion cell layer

abnormal retina ganglion layer morphology ( J:207895 )

• rods, cones and bipolar cells localize ectopically in the ganglion cell layer

abnormal retina photoreceptor layer morphology ( J:207895 )

• amacrine and ganglion cells surrounded by bipolar cells form pseudo-rosettes in the photoreceptor layer

abnormal retina outer limiting membrane morphology ( J:207895 )

• the outer limiting membrane is perturbed at the periphery of the retina at E15.5, and progressively extends to the center of the retinas where rosettes form

abnormal eye physiology ( J:207895 )

• the number of mitotic cells is increased in the retina at E17.5 and at P5

decreased retina apoptosis ( J:207895 )

• at P5, there is a decrease in the number of apoptotic cells in the retina

increased retina apoptosis ( J:207895 )

• the number of apoptotic cells is increased in the retina at E17.5

• however, at P5, there is a decrease in the number of apoptotic cells

abnormal electroretinogram waveform feature ( J:207895 )

• mice exhibit a greater reduction in amplitudes of electroretinogram responses at 1 month of age than single Crb2 conditional mutants, with both scotopic and photopic responses

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Leber congenital amaurosis 8		DOID:0110079	OMIM:613835	J:207895