Rhodopsin, 11-cis vitamin A, and interstitial retinol-binding protein (IRBP) during retinal development in normal and rd mutant mice

Carter-Dawson, Louvenia; Alvarez, Richard A.; Fong, Shao-Ling; Liou, Gregory I.; Sperling, Harry G.; Bridges, C.D.B.

doi:10.1016/0012-1606(86)90144-2

Cited by 95 publications

(41 citation statements)

References 25 publications

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“…4B, right). This indicates that they did not express IRBP, as was confirmed by staining with an anti-IRBP antibody recognizing the outer segments of photoreceptor cells (Carter-Dawson et al 1986) (Fig. 4C).…”

Section: Retinoblastoma Has Characteristics Of the Inner Nuclear Layermentioning

confidence: 83%

p107 is a suppressor of retinoblastoma development in pRb-deficient mice

Robanus-Maandag¹,

Dekker²,

Valk³

et al. 1998

Genes Dev.

297

231

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Hemizygosity for the retinoblastoma gene RB in man strongly predisposes to retinoblastoma. In the mouse, however, Rb hemizygosity leaves the retina normal, whereas in Rb −/− chimeras pRb-deficient retinoblasts undergo apoptosis. To test whether concomitant inactivation of the Rb-related gene p107 is required to unleash the oncogenic potential of pRb deficiency in the mouse retina, we inactivated both Rb and p107 by homologous recombination in embryonic stem cells and generated chimeric mice. Retinoblastomas were found in five out of seven adult pRb/p107-deficient chimeras. The retinal tumors showed amacrine cell differentiation, and therefore originated from cells committed to the inner but not the outer nuclear layer. Retinal lesions were already observed at embryonic day 17.5. At this stage, the primitive nuclear layer exhibited severe dysplasia, including rosette-like arrangements, and apoptosis. These findings provide formal proof for the role of loss of Rb in retinoblastoma development in the mouse and the first in vivo evidence that p107 can exert a tumor suppressor function.

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Section: Retinoblastoma Has Characteristics Of the Inner Nuclear Layermentioning

confidence: 83%

p107 is a suppressor of retinoblastoma development in pRb-deficient mice

Robanus-Maandag¹,

Dekker²,

Valk³

et al. 1998

Genes Dev.

297

231

View full text Add to dashboard Cite

show abstract

“…Transgenic mice containing an IRBP-chloramphenicol acetyltransferase (CAT) transgene show CAT activity in the retina as early as El3 (A1-Ubaidi et al 1992). In addition, the IRBP protein has been shown by immunohistochemistry to be produced in murine retinoblasts by El6 (Carter-Dawson et al 1986). The mitotic activity of rods peaks on the day of birth and terminates by P5 (Young 1985;Wang et al 1992).…”

Section: Discussionmentioning

confidence: 99%

Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53.

Howes¹,

Ransom²,

Papermaster³

et al. 1994

Genes Dev.

289

201

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A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen-transforming activity is attributable, at least in part, to the inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins, we addressed the role of p53 in the development of retinoblastoma in mice. Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact. Rather than developing retinoblastomas, the retinas of these mice degenerate due to photoreceptor cell death at a time in development when photoreceptors are normally undergoing terminal differentiation. The dying cells exhibit the histological and ultrastructural features of apoptosis and contain fragmented DNA. p53 is required for the induction of apoptosis in this model, because mice expressing E7 in a p53 nullizygous background develop retinal tumors instead of undergoing retinal degeneration.

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“…From a distal cilium, an outer segment begins to form at PN6 to PN7 and reaches its mature form by PN14 (48). Spectrophotometric detection of the retinal chromophore is possible after PN6 to PN7 in the mouse (11), but by using immunocytochemistry, opsin can be detected on a few rat retinal cells as early as PN1 (24). Other components of the visual transduction apparatus are present by the end of the first postnatal week, since an antibody sensitive to light-induced phosphorylation of the opsin molecule can detect this modification at PN8 (24).…”

mentioning

confidence: 99%

“…Other components of the visual transduction apparatus are present by the end of the first postnatal week, since an antibody sensitive to light-induced phosphorylation of the opsin molecule can detect this modification at PN8 (24). IRBP has been shown to appear at embryonic day 17 and increase during and after the time of inner segment formation in mice (11), and the protein encoded by c-src appears in the processes of rods and cones, as well as in ganglion and amacrine cells, at the end of mitosis in the chick retina (41), correlating with an increase in c-src mRNA (45). While some morphological differentiation and regionalized opsin expression can occur in monolayer culture (1,2), full outer segment maturation may require interactions with other cells, such as Muller glia (2a).…”

mentioning

confidence: 99%

Opsin expression in the rat retina is developmentally regulated by transcriptional activation.

1988

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The gene for rhodopsin, the primary light sensor of the visual system, is specifically expressed in the rod photoreceptor cells of the retina. We show here that in the rat, opsin RNA first accumulates to detectable levels at postnatal day 2 (PN2) and that nascent transcripts can be detected at PN1; this is the time when peak numbers of photoreceptor cells are generated by the final division of their neuroepithelial precursors. Accumulated opsin RNA then increases to reach the adult level, 0.06% of total retinal RNA, at about PN10. The transcription rate of the opsin gene increases to a similar extent over the same time course between PN3 and adulthood, suggesting that transcriptional activation is responsible for the increase in opsin expression. We used the antibody RET-Pl to show that rhodopsin protein is also detectable at PN2 and that the number of cells expressing the protein increases with time in a central-to-peripheral gradient in the retina. This increase in the number of differentiating photoreceptors in the tissue appears to account for much of the increase in opsin gene transcription and RNA accumulation. In situ hybridization to opsin RNA shows that it is restricted to the photoreceptor layer from the time it can first be detected, at PN7. Later in development, when RET-Pl staining shifts to the photoreceptor outer segments, opsin RNA becomes localized to the inner segments, suggesting that the distributions of opsin protein and RNA are related.

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Rhodopsin, 11-cis vitamin A, and interstitial retinol-binding protein (IRBP) during retinal development in normal and rd mutant mice

Cited by 95 publications

References 25 publications

p107 is a suppressor of retinoblastoma development in pRb-deficient mice

p107 is a suppressor of retinoblastoma development in pRb-deficient mice

Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53.

Opsin expression in the rat retina is developmentally regulated by transcriptional activation.

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