Foxn1nu
Spontaneous Allele Detail
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| Nomenclature |
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Symbol:
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Foxn1nu
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Name:
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forkhead box N1;
nude
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MGI ID: |
MGI:1856108 |
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Synonyms: |
Foxnlnu, hairless, nu, Whn- |
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Gene:
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Foxn1
Location:
Chr11:78357577-78386558 bp, - strand
Genetic Position: Chr11,
46.74 cM
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Control and Foxn1nu/Foxn1nu
Show the 1 image(s) involving this allele.
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Mutation
origin |
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Strain of Origin:
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albino stock
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Mutation
description |
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Allele
Type: | |
Spontaneous |
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Mutation: | |
Intragenic deletion |
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Mutation details: 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. (J:21194)
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Inheritance: | |
Recessive |
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Phenotypes
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View phenotypes for all genotypes (concatenated display).
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Disease models
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| Find Mice (IMSR) |
Mouse strains and cell lines available from the
International Mouse Strain Resource
(IMSR)
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Notes |
Dr. N.R. Grist found a hairless mutation in mice in the Virus Laboratory, Ruchill Hospital, Glasgow, and passed it on to the Institute of Animal Genetics at Edinburgh for study. Homozygotes are hairless from birth and most die within a few weeks after weaning (J:30772). Body growth rate,viability, and fertility are severely reduced. Hair follicles are normal at birth, but keratinization, which normally occurs in the middle third of the follicle, is faulty and the hairs do not erupt (J:5043). Epidermal keratinization is also faulty (J:466). Application of exogenous keratinocyte growth factor (fibroblast growth factor 7; see Fgf7) normalizes the follicular defect in Hfh11nu/Hfh11nu mice (J:27782). The growth retardation and ossification defects in Hfh11nu homozygous mice was attributed to athymia (J:12665), rather than to hairlessness per se (J:20342).
The thymus is almost totally absent (J:5059) due to failure of development of the thymic anlage which arises from the ectoderm of the third pharyngeal pouch. The rudiment remains small and cystic. Another derivative of the third pharyngeal pouch, the parathyroid, is unaffected by the nude mutation (J:6363). Differentiation of the stroma of the thymus into cortical and medullary parts, as recognized by monoclonal antibodies, occurs by embryonic day 13 in wild-type mice. This differentiation does not occur in Hfh11nu/Hfh11nu mice (J:7898). Transplantation studies have shown that the thymic rudiment of Hfh11nu/Hfh11nu mice fails to attract lymphoid cells, but that lymphoid cells of these mice are quite normal in their ability to populate implanted normal thymuses (J:11959). The thymic rudiment can engender some T-cell subpopulations and produce some factors with important functions (J:30766).
Heterozygotes (Hfh11nu/+) have a thymus about 50 to 80% as large as that of +/+ congenic controls, the size of the difference depending on strain background. The two genotypes can be distinguished by this criterion (J:7330). Hfh11nu/+ mice also show a greater susceptibility to ocular infection with Herpes simplex virus infection than do +/+ mice (J:12543).
Lack of the thymus in homozygotes leads to many defects of the immune system, including depletion of lymphocytes from thymus-dependent areas of lymph nodes and spleen, a much reduced lymphocyte population composed almost entirely of B-cells, relatively normal IgM response to thymus-independent antigens, very poor response to thymus-dependent antigens including failure to reject allogeneic and xenogeneic skin and tumor grafts, and greatly increased susceptibility to infection (J:11959).
B cells and bone marrow stem cells are also depressed in nude mice, partly as a secondary effect of the T-cell defect. Peripheral progenmitors of mononuclear phagocytes and granulocytes are, however, abundant, and phagocytic systems are the major defense against infection (J:30766).
Viability and fertility of nude mice can be greatly increased by protecting them from infectious organisms, as under specific pathogen-free or germ-free conditions (J:30766). Nude mice are widely used as naturally thymectomized mice in investigations of the role of the thymus in immune reactions.
Because of its athymia and its failure to reject xenogeneic grafts, the nude mouse has also been used as a recipient for in vivo culture and study of such grafts. As Holub (J:30766) points out, the proportion of nude mouse papers devoted to studies of the mutation, as opposed to those in which the mouse is used as an athymic culture medium, has sharply declined over time. The nude mouse is regarded as thoroughly understood, and therefore usable as a research tool. Lacunae in the knowledge of the nude mutation still do exist, however. The present revue will largely disregard the extensive literature on nude mice used as tools, and will concentrate on the biology of nude.
Various endocrine disorders have been described in nude mice (J:30766). A blunting of the hypothalamus-pituitary-adrenal axis response to stress stmuli has been described that occurs at both the pituitary and adrenal levels (J:12543).
The nude mouse may prove to be an interesting neurophysiological model, with reductions in various central nervous system components (J:30766). Microglial cell counts in the supraventricular corpus callosum are less in nude than in normal mice (J:20954). However, cerebellar Purkinje cell and granule cell populations due not seem to be reduced in nude animals (J:20471).
Flanagan (J:5043) showed linkage of the nude mutation with Re and Pmp22 on linkage group VII. Recent studies have refined the mapping with respect to successively closer mouse genes (J:4562)(J:1905), and to microsatellite loci (J:24223). As noted above, physical and transcriptional maps have further refined the location of the mutation, making positional cloning possible (J:28409)
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| References |
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Original: |
J:30772
Isaacson JH et al.,
"Two new 'hairless' mutants - Sha and Hfh11"
Mouse News Lett 1962;27():31
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All: |
281 reference(s)
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