Postnatal Lethality of P-Cadherin/Desmoglein 3 Double Knockout Mice: Demonstration of a Cooperative Effect of these Cell Adhesion Molecules in Tissue.

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Postnatal Lethality of P-Cadherin/Desmoglein 3 Double Knockout Mice: Demonstration of a Cooperative Effect of these Cell Adhesion Molecules in Tissue Homeostasis of Stratified Squamous Epithelia Jennifer M. Lenox, Peter J. Koch, My G. Mahoney, Melanie Lieberman, John R. Stanley, Glenn L. Radice Journal of Investigative Dermatology Volume 114, Issue 5, Pages 948-952 (May 2000) DOI: 10.1046/j.1523-1747.2000.00976.x Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Distribution of classical and desmosomal cadherins in oral mucosa of neonatal mice. Immunofluorescence of palate from wild-type (a, c, e) and P-cadherin/Dsg3 double mutant mice (b, d, f). P-cadherin (a) and Dsg3 (c) are expressed throughout the normal oral mucous epithelium and absent in the P-cadherin/Dsg3 double mutant specimen (b, d), whereas E-cadherin is expressed in a similar pattern in both normal and mutant epithelium (e, f). Scale bar: 50 μm. Journal of Investigative Dermatology 2000 114, 948-952DOI: (10.1046/j.1523-1747.2000.00976.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 P-cadherin/Dsg3 double mutant neonates are viable. (a) Schematic diagram of the genotyping strategy and (b) PCR products representing the different genotypes visualized on an ethidium-bromide-stained agarose gel. Arrows represent the relative positions of oligonucleotide primers used to amplify the specific alleles. The expected sizes of the PCR products are indicated. Coding exons are represented by closed boxes. The different PCAD, DSG3 genotypes are represented on the gel. kb, kilobases; m, markers. Journal of Investigative Dermatology 2000 114, 948-952DOI: (10.1046/j.1523-1747.2000.00976.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Histology of posterior tongue and palate of single and double mutant pups. Oral mucous membranes of PCAD–/–; DSG3+/+ (a, c) and PCAD–/–; DSG3–/– (b, d) pups 2 d after birth. Loss of P-cadherin alone has no effect on the structural integrity of the epithelium, whereas the double mutants display typical oral lesions observed in Dsg3 mutant mice. An early lesion (b) in the palate of a double mutant shows the basal cells separated from the suprabasilar epithelium (arrow). Re-epithelialization (arrow) and severe inflammation are observed in this advanced lesion (d), which prevents the pup from feeding normally. Scale bar: 40 μm. Journal of Investigative Dermatology 2000 114, 948-952DOI: (10.1046/j.1523-1747.2000.00976.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Ultrastructure of cell-cell contacts between basal keratinocytes. Oral basilar epithelium of PCAD–/–; DSG3+/+ (a) and PCAD–/–; DSG3–/– (b) neonates. Loss of P-cadherin alone (a) has no effect on desmosomal structure (arrow); in contrast, the double mutants (b) display the typical separation of desmosomes (double arrows) observed in Dsg3 only mutant animals. The overall ultrastructure of regions of cell-cell contact including desmosomes appears similar to that of the Dsg3 mutation alone. Scale bar: 500 nm. Journal of Investigative Dermatology 2000 114, 948-952DOI: (10.1046/j.1523-1747.2000.00976.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions