Tabby is a spontaneous mouse mutation that was discovered in 1952 (Falconer, 1952). Homozygous females and hemizygous males have defects in teeth, hair and some glands. The phenotype is variable and affected by the genotype of the mice. Incisors may be missing or reduced in size; the relative amount of enamel may also be increased. The first molar is generally smaller than wild type with reduced number of cusps (average 3.8 compared to wild type 6). The second molar may be reduced and the third molar is often, although not always, absent (Grüneberg 1965, 1966; Pispa et al, 1999). Homozygotes are viable, but because of the tooth phenotype they need a soft diet.
During embryogenesis tooth development starts normally with budding of the tooth epithelium. However, already at E13 the bud is smaller in the mesiodistal axis, and as development proceeds the tooth abnormality increases. The enamel knot forms and expresses several known signalling molecules, but is small compared to wild type (Sofaer, 1969; Pispa et al, 1999; Laurikkala et al, 2001).
Of the four different hair follicle types that mice normally have, Tabbies lack three. The remaining hairs resemble abnormal awls. Several glands are missing or reduced , e.g. sweat glands, lacrimal system glands and the salivary gland (Grüneberg, 1971).
The mutated gene is located in the X chromosome and encodes a type II transmembrane protein with a TNF domain and a short collagen-like Gly-X-Y repeat in its extracellular region. The protein has been named ectodysplasin. There are six different splicing forms, of which four contain the TNF domain. The significance of the truncated forms is not known (Srivastava et al, 1997; Ferguson et al, 1997; Mikkola et al, 1999). The two longest forms differ from each other by a deletion of two amino acids. However this changes the specificity of the proteins for the receptor so that the A1 form binds the TNF receptor Edar and the A2 form the XEDAR receptor (Yan et al, 2000).
Tabby is expressed during tooth morphogenesis in the epithelium from E10 to new born. It is also expressed in the developing skin, brain and early embryo. The probe used did not differentiate between the different splicing forms. (Mikkola et al, 1999; Laurikkala et al, 2001). Wnt6 induces Tabby expression in tooth explants (Laurikkala et al, 2001) and FGF10 can partially rescue Tabby tooth germs in vitro (Pispa et al, 1999).
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