STOCK Ces1c^e Foxn1^nu/J

Stock number: 003118
Product name: nude
Research areas: Dermatology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These mice carry a spontaneous, knock-out mutation at the Ces1c locus characterized by abnormal hair growth and defective development of the thymic epithelium with a lack of T cells and cell-mediated immunity.

Detailed description

Mice homozygous for Ces1c^e are viable and fertile and exhibit no apparent defect.

Ces1c^e was discovered in a screen of progeny of triethylenemelamine (TEM) treated male mice for mutations at specific loci, but appears to have pre-existed in the male. The screen employed analysis of blood and kidney homogenates by "standard starch gel electrophoresis techniques" and focused on enzymes known to differ in electrophoretic mobility between the parental strains (DBA/2J and C57BL/6J). Ces1c^e was initially thought to be a null allele, but characterization of homozygous F2 mice demonstrated presence of a faint band migrating between those of the parental strains, which was not perceived in the presence of either parental band. Thus, Ces1c^e was shown to be a hypomorphic electrophoretic variant (Soares 1979).

The two main defects of mice homozygous for the nude spontaneous mutation (Foxn1^nu, formerly Hfh11^nu) are abnormal hair growth and defective development of the thymic epithelium. Although the mice appear hairless, they are born with functional but faulty hair growth follicles. Hair growth cycles and patterns are evident especially in pigmented mice but the faulty follicles do not allow the hair to properly erupt. Homozygous pups can be identified as young as 24 hours by their lack of whiskers or poorly developed crinkled whiskers. Nude mice are also athymic caused by a developmental failure of the thymic anlage. Consequently, homozygous nude mice lack T cells and suffer from a lack of cell-mediated immunity. However there is not a defect in T-cell precursors and under the right conditions some functional mature T cells can be found especially in adult mice. Because of a defect in helper T-cell activity, responses to thymus-dependent antigens when detectable are primarily limited to IgM. Homozygous nude mice show partial defect in B cell development probably due to absence of functional T cells. Other endocrine and neurological deficiences have been reported. The use of nude mice has reduced the number of thymectomy procedures required in research projects. Females are not effective breeders. Ovulation starts late at 2.5 months and ends early at 4 months.

Development

Ces1c^e was discovered in a specific-locus mutation screen of progeny of triethylenemelamine (TEM) mutagenized male DBA/2J mice, but appears to have been a pre-existing, spontaneous mutation. Although the TEM-treated parent was unavailable for genotyping, three lines of evidence suggest he was a heterozygous carrier of the mutation: 7 of 13 (54%) of his immediate offspring were heterozygous for Ces1c^e; he was mated within 2 weeks after TEM treatment, so these progeny were generated from sperm that were either sperm or late spermatids when exposed, ruling out a clustering effect due to mutagenesis at the spermatogonial stage; and the seven Ces1c^e/+ offspring occurred among litters of three dams (Soares 1979).

Mice of a strain/stock bearing Ces1c^e, called ES-IE, were imported from Dr. Soares, then at NIEH, by Dr. Eva Eicher. The original stock was maintained by sister-brother inbreeding. In 1982, Ces1c^e/Ces1c^e males of this stock were bred to C57BL/6J females to produce embryos for cryopreservation. These heterozygous embryos were assigned Stock No. 000785. In 1995, mice were recovered from the cryopreserved embryos to generate an F2 generation, from which mice homozygous for both Ces1c^e and a (nonagouti) were selected and bred to generate embryos for cryopreservation. These embryos, which are segregating for Tyrp1^b and Myo5a^d, were designated STOCK a/a Ces1c^e/Ces1c^e and retained Stock No. 000785.

STOCK Ces1c^e/Ces1c^e Foxn1^nu/+ (Stock No. 003118) was generated by mating a STOCK a/a Ces1c^e/Ces1c^e (Stock No. 00785) female to a C57BL/6J-Foxn1^nu/Foxn1^nu male, then selecting Ces1c^e homozygotes from the F2 as colony founders. Embryos were generated for cryopreservation by crossing Foxn1^nu/+ or Foxn1^nu/Foxn1^nu females to Foxn1^nu/+ or Foxn1^nu/Foxn1^nu males at generation F4+.

Allele

Symbol: Foxn1^nu
Name: nude
MGI accession ID: MGI:1856108
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Foxn1
Marker name: forkhead box N1
Chromosome: 11
Strain of origin: albino stock
Molecular note: A single base pair (G) deletion in exon 3 introduces a frameshift and a premature stop codon. The encoded protein is predicted to terminate upstream of the DNA-binding domain.

Allele

MGI accession ID: MGI:95420
Marker symbol: Ces1c
Marker name: carboxylesterase 1C
Chromosome: 8