Retinoblastoma Gene Promoter Directs Transgene Expression Exclusively to the Nervous System
Bibliographic record
Abstract
In human, germ line mutations in the tumor suppressor retinoblastoma (Rb) predispose individuals to retinoblastoma, whereas somatic inactivation of Rb contributes to the progression of a large spectrum of cancers. In mice, Rb is highly expressed in restricted cell lineages including the neurogenic, myogenic, and hematopoietic systems, and disruption of the gene leads to specific embryonic defects in these tissues. The symmetry between Rb expression and the defects in mutant mice suggest that transcriptional control of Rb during embryogenesis is pivotal for normal development. We have initiated studies to dissect the mechanisms of transcriptional regulation of Rb during development by promoter lacZ transgenic analysis. DNA sequences up to 6 kilobase pairs upstream of the mouse Rb promoter, isolated from two different genomic libraries, directed transgene expression exclusively to the developing nervous system, excluding skeletal muscles and liver. Expression of the transgene in the central and peripheral nervous systems, including the retina, recapitulated the expression of endogenous Rb during embryogenesis. A promoter region spanning approximately 250 base pairs upstream of the transcriptional starting site was sufficient to confer expression in the central and peripheral nervous systems. To determine whether this expression pattern was conserved, we isolated the human Rb 5' genomic region and generated transgenic mice expressing lacZ under control of a 1.6-kilobase pair human Rb promoter. The human Rb promoter lacZ mice also expressed the transgene primarily in the nervous system in several independent lines. Thus, transgene expression directed by both the human and mouse Rb promoters is restricted to a subset of tissues in which Rb is normally expressed during embryogenesis. Our findings demonstrate that regulatory elements directing Rb expression to the nervous system are delineated within a well defined core promoter and are regionally separated from elements, yet to be identified, that are required for expression of Rb in the developing hematopoietic and skeletal muscle systems.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".