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Profile of messenger RNA decay in the Emory mouse lens in cataractogenesis and in aging
1Laboratory for Molecular Genetics, University of Southern California School of Dentistry, Los Angeles.
Abstract:
The Emory mouse is presumed to be a model for studies on human senile cataracts. The cataract develops in 5-8 months after birth, and it does not appear to have an osmotic component. To date, no specific metabolic lesion has been uncovered as a probable cause to this cataract. Several studies have shown that the Emory mouse undergoes accelerated aging changes, possibly leading to development of senile-type cataracts. In this study we quantitated changes that might occur in the population of various mRNAs for proteins presumed to be essential for lens transparency, and for proteins that may contribute to development of cataracts. By Northern blot hybridization analysis we quantitated the mRNAs for: alpha A-crystallin, beta B1-crystallin, gamma-crystallin, the main lens intrinsic membrane protein, MP26, and aldose reductase; all in lenses of Emory mouse early cataract strain (EMEC), and of an age-matched cataract resistant strain (CR). These measurements were done in increments of 1 month over a 6-month period, then at both 9 and 12 months. The results show that all of these mRNAs decrease with age and with development of cataracts; although in some cases the initial concentrations at 1 month appear to be lower in the EMEC than in the CR strain. The most dramatic change occurred with the MP26 mRNA. In the CR strain, MP26 mRNA maintained its high concentration for a period of about 6 months before it began its decline to the 12 month level (about 25% of the 1 month level).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The Emory mouse model shows decreased mRNA levels for key lens proteins, including MP26, correlating with cataract development and accelerated aging. This suggests a molecular basis for senile cataracts in this model.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- The Emory mouse (EMEC) is a model for human senile cataracts, developing cataracts around 5-8 months without an osmotic cause.
- Accelerated aging in EMEC mice is suspected to contribute to cataract formation.
- No specific metabolic defect has been identified as the cause of EMEC cataracts.
Purpose of the Study:
- To quantify changes in messenger RNA (mRNA) populations for proteins crucial to lens transparency and cataract development in EMEC mice.
- To compare mRNA levels in EMEC mice with an age-matched, cataract-resistant (CR) strain.
Main Methods:
- Northern blot hybridization was used to analyze mRNA levels.
- Quantification of mRNAs for alpha A-crystallin, beta B1-crystallin, gamma-crystallin, MP26, and aldose reductase.
- Measurements were taken monthly for 6 months, and then at 9 and 12 months in both EMEC and CR mice.
Main Results:
- All measured mRNAs generally decreased with age and cataract development in EMEC mice.
- Some mRNA concentrations were lower at 1 month in EMEC compared to CR mice.
- MP26 mRNA showed the most significant decline, dropping to about 25% of the initial level by 12 months in the CR strain.
Conclusions:
- Age-related decreases in specific lens protein mRNAs, particularly MP26, are associated with cataract development in the Emory mouse model.
- These molecular changes may underlie the development of senile cataracts in this model.
- Further research into these mRNA alterations could elucidate mechanisms of human cataractogenesis.