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Enlargement of the globe with ocular malformations in c-Myc transgenic mice
K Ishibashi1, H Yamamoto, M Hatano
1Department of Developmental Genetics, Chiba University Graduate School of Medicine, Japan.
Purpose:
To study the ocular development in transgenic mice carrying the mouse c-myc gene under the control of the Mx gene promoter (Mx-c-myc).
Methods:
Transgenic mice were generated by standard techniques. For histological studies, the tissues were fixed with 10% buffered formalin, embedded in paraffin according to the standard procedure and sliced in 4-microm sections. c-Myc expression was investigated by reverse transcriptase-polymerase chain reaction and Southern blot analysis.
Results:
A line of the Mx-c-myc mice displayed progressive enlargement of the globe with other ocular malformations. Histologically, the enlarged eyes exhibited closed cornea-iris angle, microphakia, corneal epithelial disorders, and attenuation of the inner retinal layers. Developmental analysis of eyes from these Mx-c-myc mice revealed irregular development of the iris and ciliary body at embryonic day 15.5 and the closed angle at 1 week of age. Leaky exogenous c-myc expression was detected in cornea, iris, lens, and retina from the Mx-c-myc mice by reverse transcriptase-polymerase chain reaction and Southern blot analysis. No other developmental abnormalities were observed in the Mx-c-myc mice. The anterior segment of the enlarged eyes showed the closed angle with elongation of the iris and ciliary body. There was no attenuation in the outer retinal layers from the outer plexiform layer to the retinal pigment epithelium.
Conclusions:
We conclude that the buphthalmos and accompanying changes were not due to expression of the exogenous c-myc in cornea and retina but may be the secondary changes of elevated intraocular pressure. We suggest that Mx-c-myc mice can serve as a useful model for investigating the development of the anterior segment and the genesis of buphthalmos.
Insights
Transgenic mice with the Mx-c-myc gene developed buphthalmos, characterized by enlarged eyes and anterior segment malformations. These changes are likely due to elevated intraocular pressure, not direct c-myc expression.
Area of Science:
- Ophthalmology
- Genetics
- Developmental Biology
Background:
- The role of c-myc in ocular development is not fully understood.
- Transgenic mouse models offer insights into gene function and developmental processes.
Purpose of the Study:
- To investigate ocular development in transgenic mice expressing mouse c-myc under the Mx gene promoter (Mx-c-myc).
Main Methods:
- Generation of Mx-c-myc transgenic mice.
- Histological analysis of ocular tissues.
- Reverse transcriptase-polymerase chain reaction and Southern blot analysis for c-myc expression.
Main Results:
- Mx-c-myc mice exhibited progressive globe enlargement (buphthalmos) and ocular malformations.
- Histology revealed closed cornea-iris angle, microphakia, and inner retinal layer attenuation.
- Leaky c-myc expression was detected in multiple ocular tissues.
Conclusions:
- Buphthalmos in Mx-c-myc mice is likely secondary to elevated intraocular pressure.
- Mx-c-myc mice serve as a valuable model for studying anterior segment development and buphthalmos.