The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Mapping of a major genetic modifier of embryonic lethality in TGFβ1 knockout mice
Abstract
The transforming growth factor beta 1 (TGF beta 1) signalling pathway is important in embryogenesis and has been implicated in hereditary haemorrhagic telangiectasia (HHT), atherosclerosis, tumorigenesis and immunomodulation. Therefore, identification of factors which modulate TGF beta 1 bioactivity in vivo is important. On a mixed genetic background, approximately 50% Tgfb1-/- conceptuses die midgestation from defective yolk sac vasculogenesis. The other half are developmentally normal but die three weeks postpartum. Intriguingly, the vascular defects of Tgfb1-/- mice share histological similarities to lesions seen in HHT patients. It has been suggested that dichotomy in Tgfb1-/- lethal phenotypes is due to maternal TGF beta 1 rescue of some, but not all, Tgfb1-/- embryos12. Here we show that the Tgfb1-/- phenotype depends on the genetic background of the conceptus. In NIH/Ola, C57BL/6J/Ola and F1 conceptuses, Tgfb1-/- lethality can be categorized into three developmental classes. A major codominant modifier gene of embryo lethality was mapped to proximal mouse chromosome 5, using a genome scan for non-mendelian distribution of alleles in Tgfb1-/- neonatal animals which survive prenatal lethality. This gene accounts for around three quarters of the genetic effect between mouse strains and can, in part, explain the distribution of the three lethal phenotypes. This approach, using neonatal DNA samples, is generally applicable to identification of loci that influence the effect of early embryonic lethal mutations, thus furthering knowledge of genetic interactions that occur during early mammalian development in vivo.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“preclinical studies highlight extensive influences of germline genetic modifiers of TGF-β activity on tumorigenesis, vascular integrity and allergy392,398–400.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [399]
Citations
Cites
Lander, E. S., Green, P., Abrahamson, J., Barlow, A., Daly, M. J., Lincoln, S. E., & Newberg, L. A. (1987) · Genomics · doi:10.1016/0888-7543(87)90010-3 · Cited by 6,657
Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results
Lander, E. S., & Kruglyak, L. (1995) · Nature Genetics · doi:10.1038/ng1195-241 · Cited by 5,236
Genetic Dissection of Complex Traits
Lander, E. S., & Schork, N. J. (1994) · Science · doi:10.1126/science.8091226 · Cited by 3,425
Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., Calvin, D., et al. (1992) · Nature · doi:10.1038/359693a0 · Cited by 2,985
Liu, J.-P., Baker, J. C., Perkins, A. S., Robertson, E. J., & Efstratiadis, A. (1993) · Cell · doi:10.1016/s0092-8674(05)80084-4 · Cited by 2,854
Inactivation of the Type II TGF-β Receptor in Colon Cancer Cells with Microsatellite Instability
Markowitz, S. D., Wang, J., Myeroff, L. L., Parsons, R. E., Sun, L., Lutterbaugh, J., Fan, R. S., Zborowska, E., Kinzler, K. W., Vogelstein, B., et al. (1995) · Science · doi:10.1126/science.7761852 · Cited by 2,267
Kulkarni, A. B., Huh, C. G., Becker, D., Geiser, A., Lyght, M., Flanders, K. C., Roberts, A. B., Sporn, M. B., Ward, J. M., & Karlsson, S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.770 · Cited by 1,967
McAllister, K. A., Grogg, K. M., Johnson, D. W., Gallione, C. J., Baldwin, M. A., Jackson, C. E., Helmbold, E. A., Markel, D. S., McKinnon, W. C., Murrel, J., et al. (1994) · Nature Genetics · doi:10.1038/ng1294-345 · Cited by 1,475
Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin
George, E. L., Georges‐Labouesse, E., Patel, R., Rayburn, H., & Hynes, R. O. (1993) · Development · doi:10.1242/dev.119.4.1079 · Cited by 1,305
Targeted Disruption of Mouse EGF receptor: Effect of Genetic Background on Mutant Phenotype
Threadgill, D. W., Dlugosz, A. A., Hansen, L. A., Tennenbaum, T., Lichti, U., Yee, D., LaMantia, C., Mourton, T., Herrup, K., Harris, R. C., et al. (1995) · Science · doi:10.1126/science.7618084 · Cited by 1,179
Cited by
Sorted by citations
Targeting the TGFβ signalling pathway in disease
Akhurst, R. J., & Hata, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3810 · Cited by 1,466
Self-citationTGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944
Self-citationTransforming growth factor-beta: Vasculogenesis, angiogenesis, and vessel wall integrity
Pepper, M. S. (1997) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(96)00048-2 · Cited by 737
Kyriakides, T. R., Zhu, Y.-H., Smith, L. T., Bain, S. D., Yang, Z., Lin, M. T., Danielson, K. G., Iozzo, R. V., LaMarca, M. E., McKinney, C. E., et al. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.140.2.419 · Cited by 503
Arthur, H. M., Ure, J. M., Smith, A. J. H., Renforth, G. L., Wilson, D. I., Torsney, E., Charlton, R., Parums, D. V., Jowett, T., Marchuk, D. A., et al. (2000) · Developmental Biology · doi:10.1006/dbio.1999.9534 · Cited by 448
Metadata
- Authors
- Bonyadi, M., Rusholme, S. A. B., Cousins, F. M., Su, H. C., Biron, C. A., Farrall, M., & Akhurst, R. J.
- Affiliations
- University of Glasgow (GB)
- University of Oxford (GB)
- Brown University (US)
- Centre for Human Genetics (GB)
- Corresponding author
- Akhurst, Rosemary J.
- Venue
- Nature Genetics
- Published
- 1997-02
- Volume
- 15
- Issue
- 2
- Pages
- 207-211
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2064113953
- Cited by
- 166
- References
- 34
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 4 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 7
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- TGF-β1, embryonic lethality, genetic modifiers, hereditary hemorrhagic telangiectasia, chromosome 5, genetic background, genome scan, mouse strains
- MeSH terms
- Animals, Chromosome Mapping, Crosses, Genetic, Fetal Death, Embryonic and Fetal Development, Genes, Lethal, Hematopoiesis, Mice, Inbred C57BL, Phenotype, Yolk Sac, Transforming Growth Factor beta, Mice, Knockout, Microsatellite Repeats, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
