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B6.CXB1-Pde6brd10/J

B6.CXB1-Pde6brd10/J

Carrying the rd10 mutation in Pde6b gene, B6.CXB1-Pde6brd10/J would have abnormality in the β subunit in their phosphodiesterase (PDE), which is a peripheral membrane enzyme participating in the phototransduction cascade of rod photoreceptors. Therefore, this transgenic moel would experience various retinal pathologies, especially in the photoreceptor population in the outer nuclear layer, such as the progressive degeneration in rod photoreceptor and progressive decrement in rod and cone ERG a- and b- waves.

The pathological phenotype induced by the mutation mimick retinitis pigmentosa and it has a later onset and milder severity than other model such as rd1, it might be a suitable experimental drug therapy model for retinitis pigmentosa.

Add Animal Model Information


Genetics

  • B6.CXB1-Pde6brd10/J carry a spontaneous missense point mutation named retinal degeneration 10(rd10) in their Pde6b gene, which encodes for the β subunit in phosphodiesterase (PDE).(The Jackson Laboratory)
  • rd10 is akin to rd1, but induces less severe retinal degeneration with later onset, and therefore might act as a more appropriate experimental drug therapy model for retinitis pigmentosa.(The Jackson Laboratory)
  • Suggested Control: C57BL/6J(The Jackson Laboratory)

Retinopathy

  • Pde6b, which is the gene carrying the rd10 mutation, encodes for the β subunit of posphodiesterase (PDE), which is a peripheral membrane enzyme participate in the phototransduction cascade of rod photoreceptors.(The Jackson Laboratory)
  • Therefore, it is very likely that rd10 is the cause of progressive outer nuclear layer degeneration in rod photoreceptor in the mutant, which onset at 16 days in central retina and onset at 20 days in peripheral retina, as shown by the histological analyses and supported by the nuclei counts.(The Jackson Laboratory)(MGD)
  • There is no remaining photorecptor by 60 days.(MGD)
  • These is probably one of the reason why mutations in PDE are linked with night blindness and retinitis pigmentosa.
  • mice homozygous for rd10 also exhibit:
    Sclerotic retinal vessels at 4 weeks(MGD)
    and progressive decrement in rod and cone ERG a- and b- waves(The Jackson Laboratory)
  • Nonetheless, the inner nuclear layers, which do not contain photoreceptor, are not affected.(MGD)
  • If mice are raised in complete darkness, their retinal degeneration is postponed by about 1 week.(The Jackson Laboratory)
  • Tauroursodeoxycholic acid can also decelerate the onset of degeneration in photoreceptors and retinal outer nuclear layers.(MGD)

Electrophysiology

  • Progressive decrement in rod and cone ERG a- and b- waves are exhibited in mice homozyous for rd10(The Jackson Laboratory)
  • Nonetheless, the ERG a- and b- wave amplitudes can be increased with the tauroursodeoxycholic acid treatment.(MGD)
  • Weaker cone and rod responses are exhibited in mutant under both light and dark-adapted conditions(MGD)
  • Only at the brightest flash intensity can a small a-wave be induced, which indicate the loss of sensitivity in the dark-adapted 30 days old mouse.(MGD)

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