Mammary gland, limb and yolk sac defects in mice lacking Tbx3,the gene mutated in human ulnar mammary syndrome
Abstract
Spontanteous mutations in the T-box gene TBX3, result in the human ulnar-mammary syndrome, a dominant developmental disorder characterized by abnormal forelimb and apocrine gland development. In order to develop a mouse model to study the role of this gene during development and disease, we produced a mutation in the mouse ortholog, Tbx3. The phenotype of the mutant mice verifies the role of this gene in limb and mammary gland development, and, in addition, reveals a previously unknown role for the gene in the yolk sac, a fetal membrane that is the site of hematopoiesis and is essential for survival during gestation. In homozygous mutant embryos, the yolk sac undergoes cell death and degeneration at midgestation and the fetuses die over a range of several days; none survive to birth. Tbx3 is the first T-box gene implicated in yolk sac development. Homozygous embryos show a deficiency of mammary gland induction, and exhibit both forelimb and hindlimb abnormalities. Although heterozygous mice, unlike their heterozygous human counterparts, have no apparent phenotype in limb or mammary gland, the homozygous defects in the development of these organs represent more severe manifestations of the defects characteristic of the ulnar-mammary syndrome.
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The phenotypic features of Tbx3-/- embryos, including diminished liver size, have also been observed in another Tbx3 mutant mouse line, but such liver defects were only discussed as an effect of deficiencies in yolk sac or hematovascular development.
“The phenotypic features of Tbx3 -/-embryos, including a diminished liver size, have also been observed in another Tbx3 mutant mouse line, but such liver defects were only discussed as an effect of deficiencies in the yolk sac or in hematovascular development (Davenport et al., 2003).”
From Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing <i>p19ARF</i> expression (2008) · cites this paper as Davenport et al., 2003
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- Authors
- Davenport, T. G., Jerome-Majewska, L. A., & Papaioannou, V. E.
- Affiliations
- Columbia University (US)
- Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, 701 W 168th Street, New York, NY 10032,USA
- Corresponding author
- Papaioannou, Virginia E.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2003-05-15
- Volume
- 130
- Issue
- 10
- Pages
- 2263-2273
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2027593708
- Cited by
- 295
- References
- 3
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 11 · 2016: 14 · 2015: 11 · 2014: 18 · 2013: 22 · 2012: 24
- FWCI
- 17.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD33082, R01HD033082)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Keywords
- TBX3, ulnar-mammary syndrome, mammary gland development, limb development, yolk sac development, T-box genes, mouse mutants
- MeSH terms
- Abnormalities, Multiple, Animals, Embryo, Mammalian, Female, Humans, Mammary Glands, Animal, Mice, Inbred C57BL, Mutation, Phenotype, Syndrome, Yolk Sac, In Situ Hybridization, Limb Deformities, Congenital, Mice, Knockout, Gene Targeting, T-Box Domain Proteins, Mice
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