Gene mutations causing autosomal recessive retinitis pigmentosa
(ARRP) in humans have been reported in opsin,
1 theα
-
2 and β-
3 subunits of cyclic guanosine
monophosphate (cGMP) phosphodiesterase, the α- subunit of cGMP-gated
channel,
4 RPE65,
5 adenosine triphosphate
(ATP)-binding cassette transferase protein,
6 7 tubby-like
protein 1 (TULP1),
8 and cellular retinaldehyde-binding
protein.
9 The analogous group of conditions in the dog are
the progressive retinal atrophies (PRAs) and are known to occur in
several breeds of dog (see
Ref. 10 for a review). Despite investigating
genes known to cause similar retinal dystrophies in other species, the
only causal gene mutation identified before this report is that which
causes rod–cone dysplasia type 1 (
rcd1) in the Irish setter
breed.
Rcd1 is caused by an amber mutation in theβ
-subunit of the cGMP phosphodiesterase gene
(
PDE6B).
11 12 13 Mutations in the homologous gene
have been identified in the retinal degeneration (
rd)
mouse,
14 15 and a subset of autosomal recessive retinitis
pigmentosa patients.
3 16 17 18 Rcd1 is
characterized by the absence of cGMP-phosphodiesterase activity,
leading to a 10-fold increase in cGMP levels.
19 This
results in arrested development of photoreceptors followed by a
progressive rod-led photoreceptor degeneration.
20 PRA in
the collie is characterized by similar biochemical and histopathologic
changes.
21 22 23 However, breeding studies have shown the
two forms of PRA to be nonallelic,
24 leading to the
designation of the form in the collie as rod–cone dysplasia type 2
(
rcd2). Both
rcd1 and
rcd2 are
early-onset forms of PRA.