Testicular feminization (ArTfm) is a dominant spontaneous mutation on the X chromosome. Hemizygous male mice are outwardly female in appearance except that the vagina does not open until 3 months of age if at all. Male reproductive development is abnormal leading to very small testes, and the absense of vas deferens, the epididymis, and male accessory glands. Spermatogonia and Sertoli cells are present in the testes, but spermatogenesis does not proceed past meiotic prophase. Leydig cells, which normally produce androgen in males, fail to develop normally. This strain is also segregating for the tabby mutation (EdaTa) that affects both the coat color and hair pattern growth. The tabby mutation is maintained in repulsion with the testicular feminization mutation and is used as a coat color marker to assist in identifying resulting genotypes obtained from matings.
|Allele Name||testicular feminization|
|Gene Symbol and Name||Ar, androgen receptor|
|Strain of Origin||(STOCK EdaTa x Atp7aMo-blo)F1|
|General Note||ArTfm acts by causing insensitivity to androgens due to a defect in androgen-binding receptor present in cytosol and nucleus. Most responses to androgens are absent or defective in ArTfm/Y males and are not inducible by administration of androgens (J:5221, J:5532). Androgen receptor is found in kidney, submandibular gland (J:5667) and brain (J:5927). ArTfm/Y males have about 20-25 percent of normal testosterone-binding activity in brain (J:6096) and 10-20 percent in kidney.|
|Molecular Note||A frameshift mutation resulting from the deletion of a single cytosine residue generated a premature stop codon at residue 412. The nonsense mutation is expected to preclude the translation of both the DNA- and steroid-binding domains.|
|Allele Synonym(s)||Ta; Taf; TaFa; Ta3|
|Gene Symbol and Name||Eda, ectodysplasin-A|
|Strain of Origin||stock including A, C57BL, CBA, and RIII|
|General Note||This mutation arose in a strain selected for large size. Hemizygous mutant males breed satisfactorily, but homozygous mutant females are often sterile. Hemizygous mutant females are fully fertile (J:249).Hemizygous males and homozygous females are identical in phenotype with homozygous crinkled (Edaraddcr) and downless (Edardl) mice and with homozygous or heterozygous sleek (Dlslk) mice. They are characterized by absence of guard hairs and zigzags in the coat, a bald patch behind the ear, bald tail with a few kinks near the tip, reduced aperture of the eyelids, a respiratory disorder, and a modified agouti pattern (J:249). The number of vibrissae is reduced (J:14912). The incisors may be reduced or absent, and the molars are usually smaller than normal with the third molar often absent (J:5018, J:5138). There are defects of many endocrine glands. The structures affected by the mutation all arise embryologically as downgrowths of solid epithelial cords, not by invagination with a lumen or by outgrowths from deep grooves (J:5246).Hemizygous mutant females are most easily recognized if they are agouti, in which case they show transverse stripes of light-colored normal and dark tabby hair. They have normal incisors but may have mutant or intermediate-type molars (J:5138). A small proportion of heterozygous females may show some slight defects of some of the exocrine glands (J:5193).In the development of the coat of homozygous and hemizygous mutant mice, hair follicle initiation begins at 17 days of gestation, 3 days later than normal, and ends 1 or 2 days after birth, several days earlier than normal. The hairs are of only one type and resemble abnormal awls (J:12100, J:5137). By use of dermal--epidermal recombination grafts of embryonic flank skin, it was shown that EdaTa acts in the epidermis in its effects on structure of the hairs (J:6041). The effect of the mutation in preventing growth of hair on the tail may be either dermal or epidermal. The mutation may act directly on hair cells or via a diffusible product (J:7450). The phenotype of EdaTa/+ females has been extensively studied because of its relevance to the X-inactivation theory of dosage compensation (J:5018, J:5238).EdaTa and the related mutations Edaraddcr and Edardl disrupt normal development of certain epidermal derivatives, including sweat glands. Although the sensory innervation of footpad skin and the sympathetic innervation of blood vessels in the foot pad is normal in these mutants, the sympathetic fibers that normally innervate the sweat glands fail to develop (J:19910).A candidate gene for the human familial X-linked disorder hypohidrotic ectodermal dysplasia (EDA)(OMIM 305100) has been partially cloned. Eda, a candidate for which has also been cloned, is the homologous gene in the mouse, on the basis of phenotype - hypoplasia of sweat glands, teeth, and hair - and of homologous mapping. There is high sequence identity between the cloned portions of the two genes. Known Eda mutations have been identified in the candidate mouse gene. An extracellular collagenous domain of the mouse gene, not yet identified in the EDA gene, may represent the location of mutations in 85-90% of human families (J:42614). A mouse gene Eda (ectodysplasin-A) has been proposed as the site of the tabby mutations (J:44605).Exogenous epidermal growth factor can reverse phenotypic features of EdaTa mice, advancing the delayed opening of eyelids and eruption of incisors (J:42661) and inducing development of dermal ridges and functional sweat glands (J:42660). Expression of epidermal growth factor receptor is reduced in EDA and in EdaTa mice (J:33361).|
|Molecular Note||This allele is characterized by an ~ 2 kb deletion: Genomic DNA was hybridized with an exon 1 probe showing a deletion including the coding region and primers for DNA flanking exon 1 failed to amplify in a PCR assay.|
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