PMID- 10509669
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20191210
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 40
IP  - 11
DP  - 1999 Oct
TI  - Cell-specific expression of tubby gene family members (tub, Tulp1,2, and 3) in
      the retina.
PG  - 2706-12
AB  - PURPOSE: The family of tubby-like proteins (TULPs), consisting of four family
      members, are all expressed in-the retina at varying levels. Mutations within two 
      members, tub and TULP1, are known to lead to retinal degeneration in mouse and
      humans, respectively, suggesting the functional importance of this family of
      proteins in the retina. Despite a high degree of conservation in the
      carboxy-terminal region (e.g., putative functional domain of the genes) among
      family members, they are unable to compensate for one another. The purpose of
      this study was to provide a rationale for this lack of compensation by
      investigating the spatial distribution of tubby gene family members in the retina
      and to investigate the mechanism of photoreceptor cell death in tubby mice.
      METHODS: In situ hybridization using riboprobes specific for each tubby gene
      family member and immunohistochemistry for TUB and TULP1 were performed to
      determine their expression patterns in the retina of tubby and wild-type control 
      mice. The terminal dUTP nick-end labeling (TUNEL) assay was performed to detect
      apoptotic cells in the retina of tubby and wild-type control mice. RESULTS: tub
      mRNA was found to be expressed throughout the retina, with highest expression in 
      the ganglion cell layer (GCL) and photoreceptor cells. In contrast, Tulp1
      expression was observed only in photoreceptor cells and Tulp3 mRNA was expressed 
      at a moderate level only in the inner nuclear layer (INL) and GCL. The results of
      the immunohistochemical analysis paralleled those observed in the in situ
      studies. TUB immunoreactivity was most highly concentrated in the GCL, in the
      inner and outermost regions of the INL, in the outer plexiform layer (OPL), and
      in the inner segments of photoreceptor cells. Similarly, TULP1 immunoreactivity
      was observed in the OPL and inner segments of the photoreceptor cells. No
      differences in expression at the mRNA or protein level were observed for any of
      the molecules tested in tubby or wild-type mice. TUNEL-positive cells were
      detected in the ONL of tubby mice, whereas very few were seen in the same layer
      of age-matched control mice. CONCLUSIONS: Although all tubby gene family members 
      are expressed in the retina, they each have different cell-specific expression
      patterns, which may account in part for their inability to compensate for the
      loss of one family member. The photoreceptor cell death in tubby mice occurs
      through an apoptotic mechanism, which is known to be the common final outcome of 
      other forms of retinal degeneration.
FAU - Ikeda, S
AU  - Ikeda S
AD  - The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
FAU - He, W
AU  - He W
FAU - Ikeda, A
AU  - Ikeda A
FAU - Naggert, J K
AU  - Naggert JK
FAU - North, M A
AU  - North MA
FAU - Nishina, P M
AU  - Nishina PM
LA  - eng
GR  - CA-34196/CA/NCI NIH HHS/United States
GR  - EY-11996/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Eye Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tub protein, mouse)
RN  - 0 (Tulp1 protein, mouse)
RN  - 0 (Tulp2 protein, mouse)
RN  - 0 (Tulp3 protein, mouse)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Apoptosis/physiology
MH  - Eye Proteins/*genetics/metabolism
MH  - *Gene Expression
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization
MH  - In Situ Nick-End Labeling
MH  - Intercellular Signaling Peptides and Proteins
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Photoreceptor Cells, Vertebrate/cytology/physiology
MH  - Proteins/*genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Retina/cytology/*metabolism
EDAT- 1999/10/06 00:00
MHDA- 1999/10/06 00:01
CRDT- 1999/10/06 00:00
PHST- 1999/10/06 00:00 [pubmed]
PHST- 1999/10/06 00:01 [medline]
PHST- 1999/10/06 00:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2706-12.