SEQUENCE AND EXPRESSION PATTERNS OF MOUSE SPR1 - CORRELATION OF EXPRESSION WITH EPITHELIAL FUNCTION

A final event in the terminal differentiation of stratified squamous e pithelia is the formation of a cornified cell envelope, which is a com plex of several proteins cross-linked together by transglutaminases. O ne set of proteins is the family of small proline rich (SPR) proteins. In human foreskin epidermal cell envelopes, SPRs serve as cross-bridg ing proteins among the more abundant loricrin, In order to study furth er their evolution and expression, we have isolated and sequenced cDNA s encoding two mouse SPR1 proteins, SPR1a and SPR1b. Comparative seque nce analyses showed the preservation of the overall structure of mamma lian SPR1 proteins with highly conserved termini and a central peptide domain repeated 13 (SPR1a) or seven (SPR1b) times, Tissues obtained f rom mouse fetal, newborn, and adult skin were tested by Northern blot analyses, ill situ hybridization, and immunohistochemistry using an an tibody raised to a synthetic peptide corresponding to the C terminus o f the SPR1a protein, Skin expression was first detected in fetal perid erm, in anagen hair follicles of newborn and older mice, and in the th ickened epidermis of the lip and footpad, but no signal was detected i n interfollicular trunk epidermis. High levels of SPR1a expression wer e found in epithelia from the forestomach and penis, and in benign squ amous papillomas. Other epithelia expressing SPR1a include the tongue, esophagus, and vagina, Whenever detected, SPR1a positive staining was present in the spinous and granular layers. In the forestomach and pa pillomas, the periphery of cells in the cornified layer was also stain ed. Our results suggest that SPR1a participates widely in the construc tion of cell envelopes in cornifying epithelia characterized by either increased thickness or a requirement for extreme flexibility. Based o n its likely function as a cross-bridging protein in cell envelopes, w e conclude that the mechanical attributes of cell envelopes may be det ermined in part by the SPR1 content, in accordance with the specific f unction of the epithelium.