Phenotypes Associated with This Genotype

Genotype
MGI:5755292

• Allelic Composition: Pcare^tm1Kpal/Pcare^tm1Kpal
• Genetic Background: involves: C57BL/6J * C57BL/6NTac

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

vision/eye

abnormal photoreceptor connecting cilium morphology ( J:220866 )

• at 3 weeks of age, connecting cilia (CC) appear intact but lack a connection to the OS

• some CCs appear to have broken off from their IS whereas others remain attached to these structures

abnormal photoreceptor inner segment morphology ( J:220866 )

• IHC analysis revealed significant rhodopsin staining in the inner segment (IS), suggesting deficient transport of proteins to the OS

• at 3 weeks of age, packets of IS containing mitochondria are found immediately adjacent to the RPE cell layer at a significant distance from their normal location

short photoreceptor outer segment ( J:220866 )

• significantly shorter OS region at 3 weeks of age

disorganized photoreceptor outer segment ( J:220866 )

• highly disorganized outer segments as early as 3 weeks of age

• whirls of disc membranes are found in membranous structures surrounded by what appears to be plasma membranes

photoreceptor outer segment degeneration ( J:220866 )

• nearly complete loss of OS by 24 weeks of age, when the OS is only two nuclei thick

retina cone cell degeneration ( J:220866 )

• IHC analysis revealed reduced OPN1SW staining consistent with degeneration of cone OS

abnormal retina pigment epithelium morphology ( J:220866 )

• at 3 weeks of age, RPE cells show massive accumulation of undigested material

• RPE cells appear to have either increased levels of pigmentation or contain large numbers of phagosomes with disc membrane material

• necrotic RPE cells are occasionally found by 8 weeks of age

abnormal retina pigmentation ( J:220866 )

• 78% decline in 11-cis-retinal in dark-adapted homozygotes relative to wild-type controls

• only 16% of retinal pigment detected at 3 weeks of age

abnormal retina outer nuclear layer morphology ( J:220866 )

• IHC analysis revealed significant rhodopsin staining in the ONL, suggesting deficient transport of proteins to the OS

thin retina outer nuclear layer ( J:220866 )

• outer nuclear layer (ONL) thickness is reduced by ~25% as early as 4 weeks of age

• ONL thickness is rapidly and severely reduced with increasing age

• by 24 weeks, the ONL is only two nuclei thick

retina outer nuclear layer degeneration ( J:220866 )

• rapid degeneration of the ONL after 4 weeks, with 42% and 81% lost by 8 and 24 weeks of age, respectively

retina degeneration ( J:220866 )

• early-onset and rapid retinal degeneration

retina gliosis ( J:220866 )

• infiltration of the outer retina by activated microglia as early as 3 weeks of age, with increasing numbers at later time points

abnormal electroretinogram waveform feature ( J:220866 )

• only 4 week old homozygotes exhibit detectable a-waves at the highest stimulus intensities

• by 8 weeks of age, ERG responses to increasing intensities of light are virtually flat, unlike in wild-type controls

decreased a-wave amplitude ( J:220866 )

• amplitudes of both rod photoreceptor cell-evoked scotopic a-waves and cone photoreceptor cell-dependent photopic a-waves are reduced by 8 weeks of age

decreased b-wave amplitude ( J:220866 )

• amplitudes of both rod photoreceptor cell-evoked scotopic b-waves and cone photoreceptor cell-dependent photopic b-waves are reduced by 8 weeks of age

abnormal cone electrophysiology ( J:220866 )

• reduced photopic responses at 4 and 8 weeks of age

abnormal rod electrophysiology ( J:220866 )

• reduced scotopic responses at 4 and 8 weeks of age

nervous system

abnormal photoreceptor connecting cilium morphology ( J:220866 )

• at 3 weeks of age, connecting cilia (CC) appear intact but lack a connection to the OS

• some CCs appear to have broken off from their IS whereas others remain attached to these structures

increased microglial cell activation ( J:220866 )

• migration of activated microglial cells to the outer retina by 3 weeks of age, with pronounced activation at later time points

abnormal photoreceptor inner segment morphology ( J:220866 )

• IHC analysis revealed significant rhodopsin staining in the inner segment (IS), suggesting deficient transport of proteins to the OS

• at 3 weeks of age, packets of IS containing mitochondria are found immediately adjacent to the RPE cell layer at a significant distance from their normal location

short photoreceptor outer segment ( J:220866 )

• significantly shorter OS region at 3 weeks of age

disorganized photoreceptor outer segment ( J:220866 )

• highly disorganized outer segments as early as 3 weeks of age

• whirls of disc membranes are found in membranous structures surrounded by what appears to be plasma membranes

photoreceptor outer segment degeneration ( J:220866 )

• nearly complete loss of OS by 24 weeks of age, when the OS is only two nuclei thick

retina cone cell degeneration ( J:220866 )

• IHC analysis revealed reduced OPN1SW staining consistent with degeneration of cone OS

pigmentation

abnormal retina pigment epithelium morphology ( J:220866 )

• at 3 weeks of age, RPE cells show massive accumulation of undigested material

• RPE cells appear to have either increased levels of pigmentation or contain large numbers of phagosomes with disc membrane material

• necrotic RPE cells are occasionally found by 8 weeks of age

abnormal retina pigmentation ( J:220866 )

• 78% decline in 11-cis-retinal in dark-adapted homozygotes relative to wild-type controls

• only 16% of retinal pigment detected at 3 weeks of age

immune system

increased microglial cell activation ( J:220866 )

• migration of activated microglial cells to the outer retina by 3 weeks of age, with pronounced activation at later time points

hematopoietic system

increased microglial cell activation ( J:220866 )

• migration of activated microglial cells to the outer retina by 3 weeks of age, with pronounced activation at later time points

cellular

abnormal photoreceptor connecting cilium morphology ( J:220866 )

• at 3 weeks of age, connecting cilia (CC) appear intact but lack a connection to the OS

• some CCs appear to have broken off from their IS whereas others remain attached to these structures

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinitis pigmentosa 54		DOID:0110364	OMIM:613428	J:220866