The craniosynostoses are craniofacial skeletal disorders involving temporally inappropriate fusion of the cranial sutures. The syndromes originate from mutations in the membrane-bound tyrosine kinase receptor, fibroblast growth factor receptors (FGFR). Point mutations in the linker between Ig-like domains 2 and 3 of human FGFR2 are known sources of five craniosynostoses syndromes: Apert, Crouzon, Jackson-Weiss, Beare-Stevenson, and Pfeiffer. Apert syndrome is a rare autosomal-dominant disorder characterized by premature fusion of the coronal suture, mental deficiency, and brain malformations. The Apert etiological defect has been traced to one of two point mutations on chromosome 10q in humans (7q in the mouse).

A transgenic mouse model of Apert syndrome was studied. MALDI mass spectrometry was used to screen for transgene expression. Mass spectrometry provided the same data as the validated Polymerase Chain Reaction (PCR) conventional approach, and provides a rapid throughput, high-specificity method for determining construct expression.

The molecular weight of the endogenous FGFR2 protein was calculated at 81.3 kD and the addition of the myc-his tag (approximately 25 amino acids) increased the construct's mass to approximately 83.7kD. Both proteins were identified with MALDI mass spectrometry from global protein extractions of murine tail tissue.

This study provides proof of principle for MALDI protein identification in transgenic mice. Thus, mass spectrometry may allow replacement of classical PCR in the study of protein expression in genetically engineered mice. This would provide large scale, rapid, robotic protein analysis in virtually any genetically engineered animal model.