Desmosomal Mouse Null Mutants
w. PubMed search by days old
Effects of Null Mutation


Ruiz P

Bierkamp C

Bierkamp C

Isac CM

Embryos die between E10.5-16 due to heart ventricles bursting and blood flooding the pericardium. Heart fibers are less compliant. Intercalated discs show abnormal mingling of desmosomal and adherens junction components.

Embryos surviving to later stages exhibit skin phenotypes: Large intercellular spaces are seen between keratinocytes and acantholysis and necrosis occurs in the granular layer of skin resmbling epidermolytic hyperkeratosis. Desmosomes are reduced in number, lack an inner dense plaque and have few keratin filaments anchored to them. I
n the absence of plakoglobin, beta-catenin localizes to desmosomes and binds to desmoglein.

Plakoglobin is an essential component of intercalated disc and epidermal desmosomes.

Plakoglobin plays a role in segregating desmosomal and adherens junction components.

Plakoglobin is important for cardiac compliance but not for the attachment of the myofibrillar apparatus to adherens junctions.




Desmoplakin expression begins at E3.5 in the trophectoderm. Null mutants are able to form trophectoderm, a blastocoel cavity, undergo implantation and establish partial polarity. However they are small, fragile and die at the egg cylinder stage (~E6.5) due to abnomalities of extra-embryonic tissue function.

Desmosomes are few and highly unstable and the expression of many desmosomal components is reduced. Other adhesion systems and cell junctions are normal. Intermediate filaments lie at the cell periphery but are not attached to the desmosomal plaques and fail to form a network.

Rescue of the extraembryonic tissues by tetraploid morulae aggregation permits the embryos to gastrulate. They show a collapsed and deformed heart, lack of neural folds, collapsed neural tube and spinal canal defects, and poor epidermal cell-cell adhesion. In addition they hemorrhage from reduced numbers of capilliaries which have disrupted endothelial linings.

Desmoplakin is essential for intermediate filament anchorage, plakophilin alone is insufficient. The desmoplakin null phenotype however is more severe than that of K8 null mice which have normal desmosomes.

Desmoplakins are essential for desmosome assembly/ stability possibly by mediating lateral plaque protein associations. This contrasts to other members of the plakin family, in which null mutants show loss of intermediate filament association with no effect on junction stability.

Loss of desmosomes has no effect on tissue polarity differentiation, or the formation of other types of junction but is required for egg cylinder elongation and expansion.

Desmoplakin has an essential function in VE-cadherin containing capilliary endothelial junctions.

Desmoglein 3

Koch PJ

Koch PJ

Mice developed oral mucous membrane lesions similar to those found in pemphigus vulgaris patients.

Mice lose their hair in a head to the tail wave around day 20, as the hair follicles enter the resting phase of the hair growth cycle (telogen). In adults, hair is lost in patches resembling alopecia. Cystic hair follicles lacking hair shafts are seen in these areas.

Loss of cell-cell adhesion produces a tombstone appearance of keratinocytes in the basal layer and suprabasal acantholysis of the immediate layer above in stratified squamous epithelia.

Dsg 3 is critical for cell adhesion in the deep stratified squamous epithelium and for anchoring the telogen hair to the outer root sheath of the follicle.

Desmosomes are important in maintaining the normal structure and function of hair.

DSG3 is coallelic with the spontaneous recessive mutation found in balding (bal) mice, which deletes much of the Dsg cytoplasmic domain.


Desmocollin 1

Chidgey 2001

Mice display flaky skin and a punctate epidermal barrier defect. Localized legions in the fragile epidermis are a result of acantholysis in the granular layer. There is abnormal differentiation in the epidermis as indicated by overexpression of kerain 6 and 16.

After week 6, the mice display lesions similar to chronic dermatitis, and exhibit localized hair loss due to follicle degeneration.

Dsc1 is necessary for strong adhesion and maintaining the epidermal barrier. Also, it contributes to differentiation in the epidermis.