Retina International's Scientific Newsletter - Retinitis Pigmentosa GTPase Regulator

	Retina International's Scientific Newsletter
Editor's Notes from literature on Retinitis Pigmentosa GTPase Regulator (RPGR)

Recent update from: 13.06.00

RPGR

Notes

Siberian Husky
Ex 13 spliced to ex 16 in normal transcript
Shows high homology to man
Variants: normal 13-16, retina 14-14a-15-15a, testes 14-14a-15-16

Species: Canis familiaris

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (10)

RPGR

Notes

Disease process is initiated by premature apoptosis in rod cells
12 alternatively spliced isoforms
Tissue specific transcripts
Newly identified exon specifically expressed in the retina
DNA identity to mouse: 76.4%
Exon 15a is retina specific and introduces a stop codon abolishing transcription in retina of downstream exons
Lack of information of exons 16 - 19 abolish isoprenylation
Isoprenylation does not seem to be essential for function in retina
Possible explanation for retina specific phenotype: lack of exons 16 - 19 changes subcellular localisation or partners so that mutations can not take effect or will be complemented in other tissues than retina

Species: Homo sapiens

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers: Exon 14

Protein Data

Aminoacids: 646 AA (retina)

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (5)

RPGR

Notes

Alternative splicing omits exons 2, 10, 14 + 15

Species: Homo sapiens

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

: 60 kb

Exons: 19

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE: 60
	calculated:

Reference: (3)

RPGR

Notes

Contains six copies of the RCC1 related repeat defined as GTPase regulator
Underlying RP3

Species: Homo sapiens

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

cDNA: 2784 bp

Exons: 19

Primers:

Protein Data

Aminoacids: 815 AA

Molecularweight	on SDS-PAGE: 90
	calculated:

Reference: (7)

RPGR

Notes

No SSR expansion
3 new exons (15B, 15C, 18B)
Exon skipping of exon 8, 14, 15, 15B, 15C
In frame stop codons; exons 15B, 18B, 19
GCT repeat in exon 15B
Abnormally transcribed in lymphocytes

Species: Homo sapiens

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE: 200 kDa
	calculated:

Reference: (4)

RPGR

Notes

IR in Golgi apparatus
50 kb from OTC
C-terminal isoprenylation site
2 in-frame initiation codons -> 2 polypeptides
First AUG not in human
Alternative splicing
C-terminal truncated mRPGR is not found in Golgi
Same effect by deletion of isoprenylation site

Species: Mus musculus

See also:

Chromosomal localisation	in man:
	in mouse: X

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE: 78/73 kDa
	calculated:

Reference: (9)

Rpgr

Notes

Uses human intron 14 in exon 14/15 in testis
DNA identity to human: 76.4%
mRNA in testis: 3.6 kb
High molecular weight transcripts in all tissues at ~5, 9.5, 20 kb
Strongest transcription in testis, in eye relatively low
Currently 22 exons known resulting in 10 splice variants in mice all including exons 1 - 7 and 19
Exon 15a is eye specific and introduces a stop codon abolishing transcription in retina of downstream exons
Lack of information of exons 16 - 19 abolish isoprenylation
Isoprenylation does not seem to be essential for function in retina

Species: Mus musculus (domesticus)

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

mRNA: ~2.7 kb

Exons:

Primers:

Protein Data

Aminoacids: 646 (retina)

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (5)

Rpgr

Notes

Transcripts appear at E7
2 in-frame initiation codons, first is used corresponding to human RPGR
Alternative splice products
Isoprenylated, because of -CITL geranylation hypothesized
Localized in the Golgi -complex
Suggested role in Golgi transport
Widely expressed in the adult mouse with high levels in testis and brain
Small transcripts in brain, large transcripts in testis
Role in cellular differentiation
Golgi localization is not observed after deletion of C-terminus by brefeldin A or mevastatin

Species: Mus musculus (domesticus)

See also:

Chromosomal localisation	in man:
	in mouse: X near Otc

Gene Data

mRNA: 2.7-2.8-3-3.3kb

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE: 110-80/60-62 kDa
	calculated:

Reference: (8)

RPGR

Notes

Localization to Golgi apparatus
Isoprenylation site
Expressed in retina, eye, brain, embryo
Activity in cellular trafficking
Differences between brain and retina transcript

Species: Rana

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE: 55 kDa
	calculated:

Reference: (2)

RPGR

Notes

Binding affinity to PDE6D is 90 nM
Mutations in the RCC1-like domain abolish interaction with PDE6D

Species: recombinant

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (6)

RPGR

Notes

Mutations in the RCC1 domain decrease PDED binding in a thermosensitive fashion
PDED is adaptor molecule mediating RPGR association to PDE holoenzyme and subsequent involvement of RPGR in regulation of PDE
Interaction by means of prenylation epitope?
PDED binds prenylated C-terminus of PDEAB

Species: recombinant

See also:

Chromosomal localisation	in man:
	in mouse:

Gene Data

Exons:

Primers:

Protein Data

Aminoacids:

Molecularweight	on SDS-PAGE:
	calculated:

Reference: (1)

References:
1. Becker,J., Linari,M., Manson,F., Wright,A.F., Meindl,A., and Meitinger,T. The Delta Subunit Of Rod Phosphodiesterase Interacts With The RCC1 Homologous Domain Of RPGR. 1998; Invest.Ophthalmol.Vis.Sci. 39: S953
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2. Breuer,D., Schmerl,S., Deretic,D., and Swaroop,A. Cellular localization and biochemical analysis of the retinal Retitinis Pigmentosa GTPase Regulator (Rpgr) which is mutated in X-linked Retinitis Pigmentosa. 1998; Am.J.Hum.Genet. 63: A353
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3. Dry,K.L., Manson,F.D.C., Edgar,A.J., Lennon,A.A., Bergen,A.A.B., Bird,A.C., and Wright,A. Mutation Detection And Characterisation Of RPGR The Gene For X Linked Retinitis Pigmentosa (RP3). 1997; Invest.Ophthalmol.Vis.Sci. 38: S679
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4. Holinski-Feder,E., Lorenz,B., Meyer,C., D�rner,C., Herrmann,K., Ueffing,M., and Meitinger,T. The RPGR Gene in Retinitis Pigmentosa Type 3. 1998; Invest.Ophthalmol.Vis.Sci. 39: S292
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5. Kirschner,R., Zeitz,C., Knobeloch,K.-P., R�ther,K., Rohde,E., Hoffmann,K., Grosse,J., Horak,I., Roepman,R., Rosenberg,T., Cremers,F.P.M., Ropers,H.-H., and Berger ,W. X-linked retinitis pigmentosa 3 (RP3): identification of a retina-specific RPGR transcript and gene targeting of the mouse orthologue. 1999; Am.J.Hum.Genet. 65: A306
Goto Top
6. Linari,M., Ueffing,M., Manson,F., Wright,A., Meitinger,T., and Becker,J. The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. 1999; Proc.Natl.Acad.Sci.U.S.A. 96: 1315-1320.
Goto Top Link to PudMed
7. Meindl,A., Dry,K., Herrmann,K., Manson,F., Ciccodicola,A., Edgar,A., Carvalho,M.R., Achatz,H., Hellebrand,H., Lennon,A., Migliaccio,C., Porter,K., Zrenner,E., Bird,A., Jay,M., Lorenz,B., Wittwer,B., D'Urso,M., Meitinger,T., and Wright,A. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). 1996; Nat.Genet. 13: 35-42.
Goto Top Link to PudMed
8. Yan,D., Swain,P.K., Breuer,D., Tucker,R.M., Wu,W., Fujita,R., Rehemtulla,A., Burke,D., and Swaroop,A. Biochemical characterization and subcellular localization of the mouse retinitis pigmentosa GTPase regulator (mRpgr). 1998; J.Biol.Chem. 273: 19656-19663.
Goto Top Link to PudMed
9. Yan,F., Cooper,N.G., and McLaughlin,B.J. Temperature-sensitive interactions between RPE and rod outer segment surface proteins. 1998; Exp.Eye Res. 66: 783-790.
Goto Top Link to PudMed
10. Zeiss,C.J., Ray,K., Acland,G.M., and Aguirre,G.D. Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3). 2000; Hum.Mol.Genet. 9: 531-537.
Goto Top Link to PudMed

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Contact the editor: irpamp@irpa.org	This site is maintained and edited by Dr. rer. medic. Markus Preising, Dipl.Biol. Molecular Genetics Laboratory Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics University of Regensburg Head: Prof. Dr. med. Birgit Lorenz