Mouse Genome Informatics
hm
    Tulp1tm1Pjn/Tulp1tm1Pjn
involves: 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
vision/eye
• as early as 18 days of age, homozygotes display a significant increase in TUNEL-positive nuclei in the outer nuclear layer of the retina relative to wild-type mice
• by 4 weeks of age, homozygotes exhibit attenuated retinal vessels
• by 4 weeks of age, homozygotes display a granular appearing retinal pigment epithelium
• by 6 months of age, remnants of the external limiting membrane are in direct contact with the retinal pigment epithelium
• by 6 months of age, the external limiting membrane is in contact with the pigment epithelium, outer and inner segments of photoreceptors are absent, the outer plexiform layer has collapsed, and the inner nuclear layer displays intracellular and mitochondrial swelling
• at 2 weeks of age, the combined thickness of the inner and outer segment of mutant photoreceptors is only ~20% of wild-type (J:59884)
• at P12, homozygotes display ectopic localization of rhodopsin in the extracellular vesicles and inner segment plasma membranes, indicating that a substantial fraction of rhodopsin fails to reach the outer segments in mutant photoreceptors (J:70710)
• starting at 4 weeks of age, homozygotes show rapid, progressive loss of photoreceptor cells
• however, no obvious photoreceptor abnormalities are detected at 2 weeks of age
• at 2 weeks of age, the inner segment appears fragmented, as evidenced by focal formation of vesicles in this region (J:59884)
• isolated plasma membrane-bound vesicles appear to be either inner segment plasma membrane fragments or extremely swollen extruded mitochondria (J:59884)
• at P12, homozygotes display aberrant (ectopic) rhodopsin accumulation in inner segment plasma membranes and in extracellular vesicles, indicating misrouting of nascent rhodopsin (J:70710)
• by 6 months of age, the photoreceptor inner segment is absent
• by 2 weeks of age, homozygotes exhibit a shortening of the inner segment of photoreceptor cells relative to wild-type littermates
• at 2 weeks of age, the outer segment appears fragmented and the entire outer segment layer is only 20% normal thickness
• distortion of the photoreceptor lamellae due to swelling is often observed
• by 6 months of age, the photoreceptor outer segment is absent
• by 2 weeks of age, homozygotes exhibit a shortening of the outer segment of photoreceptor cells relative to wild-type littermates
• by 4 weeks of age, homozygotes show rapid, progressive loss of photoreceptor cells (J:59884)
• at P20, homozygotes are in the early stage of retinal photoreceptor degeneration (J:70710)
• by 6 months of age, the cells of the inner nuclear layer lie close to the outer nuclear layer, and moderately severe intracellular and mitochondrial swelling is observed
• homozygotes display a progressive reduction of ONL thickness starting at 2 weeks of age
• by 20 weeks of age, some regions of retina no longer contain a detectable ONL, whereas others retain a 1-2 nuclear layer thickness
• at 18 days of age, numerous TUNEL-positive nuclei are observed in the ONL of mutant mice, whereas only a few are detected in wild-type mice; no differences in ONL thickness are noted at this age
• by 4 weeks of age, numerous apoptotic nuclei are detected in the mutant ONL
• by 6 months of age, the outer plexiform layer has collapsed and synaptic complexes are not identifiable
• homozygotes display an early-onset retinal degeneration with a progressive, rapid loss of photoreceptors
• ERG recordings indicate abnormal cone-mediated responses with reduced a- and b-wave amplitudes even at the earliest age tested (19 days of age)
• deterioration of cone signals is progressive, with responses virtually non-detectable by 67 days of age (the oldest age tested)
• ERG recordings indicate abnormal rod-mediated responses with reduced a- and b-wave amplitudes even at 19 days of age
• deterioration of rod signals is progressive, with responses virtually non-detectable by 67 days of age

nervous system
• at 2 weeks of age, the combined thickness of the inner and outer segment of mutant photoreceptors is only ~20% of wild-type (J:59884)
• at P12, homozygotes display ectopic localization of rhodopsin in the extracellular vesicles and inner segment plasma membranes, indicating that a substantial fraction of rhodopsin fails to reach the outer segments in mutant photoreceptors (J:70710)
• starting at 4 weeks of age, homozygotes show rapid, progressive loss of photoreceptor cells
• however, no obvious photoreceptor abnormalities are detected at 2 weeks of age
• at 2 weeks of age, the inner segment appears fragmented, as evidenced by focal formation of vesicles in this region (J:59884)
• isolated plasma membrane-bound vesicles appear to be either inner segment plasma membrane fragments or extremely swollen extruded mitochondria (J:59884)
• at P12, homozygotes display aberrant (ectopic) rhodopsin accumulation in inner segment plasma membranes and in extracellular vesicles, indicating misrouting of nascent rhodopsin (J:70710)
• by 6 months of age, the photoreceptor inner segment is absent
• by 2 weeks of age, homozygotes exhibit a shortening of the inner segment of photoreceptor cells relative to wild-type littermates
• at 2 weeks of age, the outer segment appears fragmented and the entire outer segment layer is only 20% normal thickness
• distortion of the photoreceptor lamellae due to swelling is often observed
• by 6 months of age, the photoreceptor outer segment is absent
• by 2 weeks of age, homozygotes exhibit a shortening of the outer segment of photoreceptor cells relative to wild-type littermates
• by 4 weeks of age, homozygotes show rapid, progressive loss of photoreceptor cells (J:59884)
• at P20, homozygotes are in the early stage of retinal photoreceptor degeneration (J:70710)

cardiovascular system
• by 4 weeks of age, homozygotes exhibit attenuated retinal vessels

pigmentation
• by 4 weeks of age, homozygotes display a granular appearing retinal pigment epithelium
• by 6 months of age, remnants of the external limiting membrane are in direct contact with the retinal pigment epithelium

growth/size
N
• surprisingly, homozygotes exhibit normal body weight gain relative to control littermates, as measured at 4, 6, 9, 12 and 20 weeks of age (J:59884)

hearing/vestibular/ear
N
• surprisingly, homozygotes display normal ABR thresholds across all four test stimuli (click, 8, 16 and 32 kHz) at 4 weeks of age (J:59884)
• no significant morphological alterations are observed in the cochlea at 4 and 8 weeks of age (J:59884)

cellular
• as early as 18 days of age, homozygotes display a significant increase in TUNEL-positive nuclei in the outer nuclear layer of the retina relative to wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Retinitis Pigmentosa 14; RP14 600132 J:59884