Mouse Sprr locus: a tandem array of coordinately regulated genes

Area of Science:

• Biochemistry
• Genetics
• Dermatology

Background:

• Small Proline Rich (SPRR) proteins are key components of the cornified cell envelope, crucial for forming the skin's permeability barrier.
• The murine Sprr gene family exhibits diversification, allowing for specialized barrier formation in different tissues like skin, mouth, and tongue.
• Sprr genes are tandemly arrayed on mouse Chromosome 3, suggesting potential for coordinated regulation.

Purpose of the Study:

• To identify and characterize novel members of the murine Sprr gene family, including the ortholog of human SPRR4.
• To create a sequence-verified physical map of the Sprr gene region and determine the complete coding sequences of Sprr2 genes.
• To investigate the expression patterns of Sprr genes in a mouse model lacking the transcription factor Kruppel-like factor 4 (Klf4-/-), a model of barrier deficiency.

Main Methods:

• Sequence similarity analysis to identify novel Sprr family members.
• Physical mapping and sequencing to define the Sprr gene region and coding sequences.
• RNase protection assays to quantify gene expression in Klf4-/- mice.

Main Results:

• A novel murine Sprr gene, orthologous to human SPRR4, was identified.
• The complete coding sequences of Sprr2 genes were determined, and a physical map of the region was established.
• Twelve out of fifteen Sprr family members were found to be upregulated in Klf4-/- mice.
• Conserved regulatory elements were identified upstream of human and mouse SPRR2 genes, suggesting shared regulatory mechanisms.

Conclusions:

• The Sprr gene cluster's organization and observed misregulation in Klf4-/- mice suggest a mechanism for coordinate gene regulation.
• These findings provide insights into the genetic regulation of skin barrier formation and the role of SPRR proteins.