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Genetic Manipulation of the Mouse Developing Hypothalamus through In utero Electroporation

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Altered ion-responsive gene expression in Mmp20 null mice.

C E Tye¹, R Sharma, C E Smith

¹Department of Cytokine Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.

Journal of Dental Research

|October 9, 2010

Summary

Matrix metalloproteinase-20 (Mmp20) deficiency alters enamel pH regulation and reduces ion transporter gene expression during tooth development. This suggests a feedback mechanism controls ion-responsive gene activity in developing enamel.

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Area of Science:

Biomineralization
Dental Research
Developmental Biology

Background:

Enamel maturation involves hydroxyapatite crystallite expansion and proton release, requiring buffering by carbonic anhydrases and ion transporters.
Matrix metalloproteinase-20 (Mmp20) null mice exhibit significantly reduced enamel thickness (approx. 50%).

Purpose of the Study:

To investigate alterations in ion regulation within the enamel of Mmp20(-/-) mouse incisors.
To determine the impact of Mmp20 deficiency on enamel pH dynamics and related gene expression.

Main Methods:

pH indicator staining of wild-type and Mmp20(-/-) mouse incisors to assess enamel pH changes during development.
Quantitative analysis of ion-regulatory gene expression (Atp2b4, Slc4a2, Car6, Cftr, Odam, Klk4) in enamel organs from Mmp20(-/-) and wild-type mice.

Main Results:

Mmp20(-/-) incisors showed attenuated pH changes compared to wild-type during enamel development.
Expression of key ion-regulatory genes, including secreted carbonic anhydrase (Car6), was significantly decreased in Mmp20(-/-) enamel organs.
Expression of Odam and Klk4 remained unaffected by Mmp20 deficiency.

Conclusions:

Mmp20 plays a crucial role in regulating enamel pH homeostasis during development.
A feedback mechanism likely coordinates ion-responsive gene expression in the developing enamel organ.
Mmp20 deficiency disrupts normal ion transport and buffering systems essential for proper enamel formation.