Mice homozygous for the Dsg4lah mutation have thicker, stiffer skin and a fine scale within a few days of birth. The epidermal keratinocytes have a hyperproliferative phenotype. These mice fail to develop normal fur, and have alopecia and shortened vibrissae. Although all hair types are found, the hair is very sparse and is shorter and more rough than normal. Rather than the normal gradual transition of keratinocytes from proliferation to differentiation in the lower hair follicle, the lanceolate hair mice show a premature, abrupt switch. Above the melanogenic zone, a swelling forms that subsequently is pushed out by continued growth of the hair shaft to become the distal tip of the hair. Lanceolate hair mice take their name from the resulting lance-head shape of the hair. Homozygotes can breed, but heterozygous females are better mothers than homozygotes. Unlike Dsg4lah-J homozygotes, Dsg4lah homozygotes do not have growth re...
Mice homozygous for the Dsg4lah mutation have thicker, stiffer skin and a fine scale within a few days of birth. The epidermal keratinocytes have a hyperproliferative phenotype. These mice fail to develop normal fur, and have alopecia and shortened vibrissae. Although all hair types are found, the hair is very sparse and is shorter and more rough than normal. Rather than the normal gradual transition of keratinocytes from proliferation to differentiation in the lower hair follicle, the lanceolate hair mice show a premature, abrupt switch. Above the melanogenic zone, a swelling forms that subsequently is pushed out by continued growth of the hair shaft to become the distal tip of the hair. Lanceolate hair mice take their name from the resulting lance-head shape of the hair. Homozygotes can breed, but heterozygous females are better mothers than homozygotes. Unlike Dsg4lah-J homozygotes, Dsg4lah homozygotes do not have growth retardation. Mice homozygous for either Dsg4lah or Dsg4lah-J have elevated serum IgE. (Montagutelli et al., 1996; Sundberg et al., 2000; Kljuic et al., 2003.)
The lanceolate hair (lah) mutation, later identified as an allele of the desmoglein 4 (Dsg4) gene (Kljuic et al. 2003), was discovered during inbreeding of progeny of a chemically mutagenized mouse. 8-week old male mice of a stock homozygous for seven recessive mutations (a, Tyrp1b, p, Tyrc-ch, Ednrbs, Myo5ad and Bmp5se)(Russell 1951) were treated with ethylnitrosourea and bred to BALB/cByJ females. Several independent lines were established from these crosses by more than 10 generations of sister-brother inbreeding. Mice with alopecia were found during development of one of these lines, and a subline segregating for Dsg4lah was established by crossing homozygous males with their heterozygous sisters. After 20 generations of such inbreeding, this line became the segregating inbred strain LAH. The congenic strain CByJ.LAH-Dsg4lah was created by crossing LAH and BALB/cByJ mice, then backcrossing Dsg4lah carriers, identified by progeny testing, to BALB/cByJ mice for 4 additional generations (to N5) in the laboratory of Dr. Xavier Montagutelli at Unite de Genetique des Mammiferes, Institut Pasteur, Paris (Montagutelli et al. 1996; Montagutelli, personal communication, 1999). The strain was imported to The Jackson Laboratory by Dr. John P. Sundbergin 1996; upon their arrival, Dsg4lah/Dsg4lah males were crossed to female BALB/cByJ mice. Dr. Sundberg donated offspring of the first-generation progeny of these crosses to the Mouse Mutant Resource. After initial crosses of pairs that may have been siblings or half siblings, the strain was maintained by sister-brother inbreeding. Embryos were preserved from crosses of heterozygous females and homozygous males.
|Allele Name||lanceolate hair|
|Allele Type||Chemically induced (ENU)|
|Gene Symbol and Name||Dsg4, desmoglein 4|
|Gene Synonym(s)||CDGF13; CDHF13; HYPT6; LAH; lah; lah; lanceolate hair|
|Strain of Origin||NB|
|Molecular Note||The mutation in the lah allele was identified as an A to C transversion at nucleotide 587 within exon 6. The mutation causes a tyrosine to serine change at amino acid position 196 affecting a potential phosphorylation site.|
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