B6CBACa A^w-J/A-Plp1^jp Eda^Ta/J

Stock number: 000287
Research areas: Dermatology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Detailed description

Hemizygous males carrying the X-linked jimpy spontaneous mutation (Plp1^jp) appear normal when sitting quietly, but beginning at about 3 weeks of age they show a marked tremor of the hindquarters when attempting movement. After 3 weeks of age convulsions may occur. These males die between 20 and 40 days of age. In males, the CNS is very deficient in myelin, but the PNS is normally myelinated. Heterozygous jimpy females have normal lifespans with no overt phenotype. However, jimpy heterozygous females are reported to have reduced numbers of oligodendrocytes compared to wildtype females. While the mutation is recessive, only partial phenotypic rescue was attained by the transgenic expression of the two major isoforms, PLP and DM20, suggesting a dominant negative action from this allele (Nandon et al., 1994). This stock is also carrying the X-linked tabby mutation (Eda^Ta).

Development

The tabby (Eda^Ta) and jimpy (Plp1^jp) mutations were imported to The Jackson Laboratory together from Dr. Mary Lyon at Harwell in 1961. Tabby had arisen spontaneously in a strain selected for large size (Falconer DS 1953. Z Indukt Abstammungs-Vererbungsl 85:210-19) and jimpy arose in an inbred line (Philips RJS. 1954. Z Indukt Abstammungs Vererbungsl 86:322-6) in 1954. The imported stock was segregating for other loci but tabby and jimpy, linked and located on the X Chromosome, were maintained by sibling matings generally of the Eda^Ta Plp1^jp/+ + genotype crossed to a Ta/Y or +/Y male. In 1965 at approximately generation F6 a Eda^Ta Plp1^jp/+ + female was outcrossed to a C57BL/6J-A^w-J male and pairs were mated. At F3 a Eda^Ta Plp1^jp/+ + female was again crossed to a C57BL/6J-A^w-J male. The stock was then continually backcrossed into the C57BL/6J-A^w-J strain to N10. At N11 a cross of a Eda^Ta Plp1^jp/+ + female was made to a CBA/Ca male and in the next generation a Eda^Ta Plp1^jp/+ + female was crossed to the B6CBACa F1 hybrid male and the stock was then bred by crossing to the hybrid male each generation. It was cryopreserved in 1981 by mating Eda^Ta Plp1^jp-?/+ + females at N71 to B6CBACa-A^w-J/A F1 males.

Allele

Symbol: Plp1^jp
Name: jimpy
MGI accession ID: MGI:1856065
Generation method: Spontaneous
Marker symbol: Plp1
Marker name: proteolipid protein (myelin) 1
Chromosome: X
Strain of origin: (KLM STOCK x XY STOCK)F1
Molecular note: Sequence analysis showed that this allele carries an A-to-G base change at the 3' splice acceptor site of intron 4, eliminating the exon 5 splice acceptor site by changing it from ATG to TGG.

Allele

Symbol: A^w-J
Name: white bellied agouti Jackson
MGI accession ID: MGI:1855946
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Chromosome: 2
Strain of origin: C57BL/6J

Allele

Symbol: Eda^Ta
Name: tabby
MGI accession ID: MGI:1856197
Generation method: Spontaneous
Marker symbol: Eda
Marker name: ectodysplasin-A
Chromosome: X
Strain of origin: stock including A, C57BL, CBA, and RIII
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.
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 (Edaradd^cr) and downless (Edar^dl) mice and with homozygous or heterozygous sleek (Dl^slk) 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 Eda^Ta 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 Eda^Ta/+ females has been extensively studied because of its relevance to the X-inactivation theory of dosage compensation (J:5018, J:5238). Eda^Ta and the related mutations Edaradd^cr and Edar^dl 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 Eda^Ta 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 Eda^Ta mice (J:33361).