EurekaMag.com logo
+ Site Statistics
References:
52,725,316
Abstracts:
28,411,598
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

RPGRIP1 is essential for normal rod photoreceptor outer segment elaboration and morphogenesis


Human Molecular Genetics 18(22): 4329-4339
RPGRIP1 is essential for normal rod photoreceptor outer segment elaboration and morphogenesis
The function of the retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) gene is currently not known. However, mutations within the gene lead to Leber Congenital Amaurosis and autosomal recessive retinitis pigmentosa in human patients. In a previously described knockout mouse model of the long splice variant of Rpgrip1, herein referred to as Rpgrip1(tm1Tili) mice, mislocalization of key outer segment proteins and dysmorphogenesis of outer segment discs preceded subsequent photoreceptor degeneration. In this report, we describe a new mouse model carrying a splice acceptor site mutation in Rpgrip1, herein referred to as Rpgrip1(nmf247) that is phenotypically distinct from Rpgrip1(tm1Tili) mice. Photoreceptor degeneration in homozygous Rpgrip1(nmf247) mice is earlier in onset and more severe when compared with Rpgrip1(tm1Tili) mice. Also, ultrastructural studies reveal that whereas Rpgrip1(nmf247) mutants have a normal structure and number of connecting cilia, unlike Rpgrip1(tm1Tili) mice, they do not elaborate rod outer segments (OS). Therefore, in addition to its role in OS disc morphogenesis, RPGRIP1 is essential for rod OS formation. Our study indicates the absence of multiple Rpgrip1 isoforms in Rpgrip1(nmf247) mice, suggesting different isoforms may play different roles in photoreceptors and underscores the importance of considering splice variants when generating targeted null mutations.


Accession: 055338587

PMID: 19679561

DOI: 10.1093/hmg/ddp385



Related references

Disulfide-mediated oligomerization of Peripherin/Rds and Rom-1 in photoreceptor disk membranes. Implications for photoreceptor outer segment morphogenesis and degeneration. Journal of Biological Chemistry 275(8): 5370-5378, 2000

Effect of Rds abundance on cone outer segment morphogenesis, photoreceptor gene expression, and outer limiting membrane integrity. Journal of Comparative Neurology 504(6): 619-630, 2007

A photoreceptor-specific cadherin is essential for the structural integrity of the outer segment and for photoreceptor survival. Neuron 32(5): 775-786, December 6, 2001

ROM-1 is required for outer segment morphogenesis and photoreceptor viability. IOVS 39(4): S962, March 15, 1998

Meckelin is necessary for photoreceptor intraciliary transport and outer segment morphogenesis. Investigative Ophthalmology & Visual Science 53(2): 967-974, 2012

Morphogenesis of the photoreceptor outer segment during development of mouse retina. Zoological Science (Tokyo) 7(6): 1027, 1990

Outer segment morphogenesis in cultures of undifferentiated photoreceptor precursor cells. Investigative Ophthalmology & Visual Science 37(3): S624, 1996

Morphogenesis of the photoreceptor outer segment during postnatal development in the mouse (BALB/c) retina. Cell and Tissue Research 269(1): 39-48, 1992

Recovery of photoreceptor outer segment length and analysis of membrane assembly rates in regenerating primate photoreceptor outer segments. Investigative Ophthalmology & Visual Science 34(1): 175-183, 1993

Early defects in photoreceptor outer segment morphogenesis in zebrafish ift57, ift88 and ift172 Intraflagellar Transport mutants. Vision Research 49(4): 479-489, 2009