Related Experiment Video
Updated: May 26, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Embryonic epithelial Pten deletion through Nkx2.1-cre leads to thyroid tumorigenesis in a strain-dependent manner
Caterina Tiozzo1,2,3, Soula Danopoulos1, Maria Lavarreda-Pearce1
1Developmental Biology Program, Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, California 90027, USA.
Abstract:
Even though the role of the tyrosine phosphatase Pten as a tumor suppressor gene has been well established in thyroid cancer, its role during thyroid development is still elusive. We therefore targeted Pten deletion in the thyroid epithelium by crossing Pten(flox/flox) with a newly developed Nkx2.1-cre driver line in the BALB/c and C57BL/6 genetic backgrounds. C57BL/6 homozygous Pten mutant mice died around 2 weeks of age due to tracheal and esophageal compression by a hyperplasic thyroid. By contrast, BALB/c homozygous Pten mutant mice survived up to 2 years, but with a slightly increased thyroid volume. Characterization of the thyroid glands from C57BL/6 homozygous Pten mutant mice at postnatal day 14 (PN14) showed abnormally enlarged tissue with areas of cellular hyperplasia, disruption of the normal architecture, and follicular degeneration. In addition, differing degrees of hypothyroidism, thyroxine (T(4)) decrease, and thyroid-stimulating hormone elevation between the strains in the mutants and the heterozygous mutant were detected at PN14. Finally, C57BL/6 heterozygous Pten mutant mice developed thyroid tumors after 2 years of age. Our results indicate that Pten has a pivotal role in thyroid development and its deletion results in thyroid tumor formation, with the timing and severity of the tumor depending on the particular genetic background.
Insights
Deleting the phosphatase Pten in mice disrupts thyroid development, causing hyperplasia and tumors. The severity depends on the genetic background, impacting thyroid hormone levels and survival.
Area of Science:
- Endocrinology
- Developmental Biology
- Oncology
Background:
- The tumor suppressor gene Pten's role in thyroid cancer is known, but its function in normal thyroid development remains unclear.
- Investigating Pten's precise role is crucial for understanding thyroid pathologies.
Purpose of the Study:
- To elucidate the function of Pten during thyroid gland development.
- To determine the consequences of Pten deletion in thyroid epithelium across different genetic backgrounds.
Main Methods:
- Generated Pten-deficient mouse models by crossing Pten(flox/flox) mice with Nkx2.1-cre driver lines on BALB/c and C57BL/6 backgrounds.
- Analyzed thyroid gland morphology, thyroid hormone levels (T4), and thyroid-stimulating hormone (TSH) in mutant mice at various time points.
- Assessed tumor formation and survival rates in relation to Pten deletion and genetic background.
Main Results:
- Homozygous Pten deletion in C57BL/6 mice led to early death (2 weeks) from thyroid hyperplasia, while BALB/c mutants survived longer with mild thyroid enlargement.
- Postnatal day 14 C57BL/6 Pten mutants exhibited thyroid hyperplasia, architectural disruption, follicular degeneration, hypothyroidism, decreased T4, and elevated TSH.
- Heterozygous Pten deletion in C57BL/6 mice resulted in thyroid tumor development after 2 years.
Conclusions:
- Pten plays a critical role in regulating thyroid development and preventing hyperplasia.
- Pten deletion leads to thyroid tumor formation, with outcomes influenced by the genetic background.
- These findings highlight Pten's importance as a tumor suppressor in the thyroid and its developmental functions.
