Disease relevance of Al

• This virus, designated RA-1, elicits a syndrome in neonatal mice that includes neurological disturbances, permanent crippling of limbs, dwarfism, alopecia, blepharitis, "masking," and a rigid curvature of the thoracic spine [1].
• Transgenic mice overexpressing IL-31 developed severe pruritis, alopecia and skin lesions [2].
• The runting syndrome consisted of retarded growth, oily hair, alopecia, and steatorrhea [3].
• Alopecia areata is a tissue-restricted autoimmune disease of the hair follicle, which results in hair loss and baldness [4].
• Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice [4].

Psychiatry related information on Al

• Alopecia, a common sequel of radiation treatment of brain tumors, increases patient stress to the extent that refusal of treatment may occur [5].
• Cinnarizine, a calcium antagonist that produces parkinsonism in humans, induces behavioural changes such as alopecia, buco-lingual dyskinesia and reduction of motor activity in female parkin knock out (PK-KO) mice but not in wild-type (WT) controls [6].
• Alopecia, dyspnea and cyanosis in rats, and lethargy in both species occurred in the 0.1 to 0.2% groups [7].

High impact information on Al

• HGPS is a rare genetic disorder resulting in phenotypes suggestive of accelerated ageing, including shortened stature, craniofacial disproportion, very thin skin, alopecia and osteoporosis, with death in the early teens predominantly due to atherosclerosis [8].
• Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss) [9].
• A kindred with a rare, recessively inherited type of alopecia universalis was used to search for a locus by homozygosity mapping, and linkage was established in a 6-centimorgan interval on chromosome 8p12 (the logarithm of the odds favoring linkage score was 6.19) [10].
• Keratin 17 (K17)-null mice develop alopecia in the first week post-birth, correlating with hair shaft fragility and untimely apoptosis in the hair bulb [11].
• Metabolic and cellular analysis of alopecia in vitamin D receptor knockout mice [12].

Chemical compound and disease context of Al

• Therefore, tyrosine kinase C agonists and antagonists deserve systematic exploration for the management of hair growth disorders that are related to premature (alopecia/effluvium) or retarded catagen (hirsutism/hypertrichosis) [13].
• Minoxidil, a potent antihypertensive agent, induces generalized hypertrichosis when administered systemically, or localized hair regrowth when applied topically to sites of severe alopecia areata [14].
• In conclusion, alopecia areata-like hair loss in C3H/HeJ mice responded to treatment with the contact sensitizer squaric acid dibutylester analogous to human alopecia areata [15].
• Both systemic and topical application of 16,16 dm PGE2 protected from some degree of radiation-induced alopecia, which supports the conclusion that prostaglandins may be useful in the protection of hair follicles in patients treated with radiation for brain tumors [5].
• Transgenic mice constitutively expressing IL-7 developed severe dermatitis with erythroderma and alopecia [16].

Biological context of Al

• Immunization of mice with rPfs25 plus CpG ODN improved both the antibody titer (a 30-fold-higher antibody response than that with rPfs25-Al alone) and avidity [17].
• To identify the cell population responsible for the alopecia, we performed hair-reconstitution assays in nude mice and observed normal hair follicle morphogenesis, regardless of the VDR status of the keratinocytes and dermal papilla cells [12].
• Because hair regrowth in chemotherapy-induced alopecia is associated with follicle cell proliferation and active melanogenesis similar to that observed in the anagen phase of normal hair growth, we examined whether AdShh-mediated Shh expression would accelerate hair regrowth in the skin of mice with chemotherapy-induced alopecia [18].
• Incontinentia Pigmenti (IP) is an X-linked genodermatosis that is lethal for males and present in females with abnormal skin pigmentation and high variable clinical signs, including retinal detachment, anodontia, alopecia, nail dystrophy and nervous system defects [19].
• Effects observed include development of dermal follicular cysts, excessive skin wrinkling, enhanced nail growth, alopecia, and spontaneous tumor development [20].

Anatomical context of Al

• AdShh treatment of 3-week-old mice with cyclophosphamide-induced alopecia was followed by accelerated hair follicle recovery (19 of 22 mice); such recovery was not observed at this rate in AdNull-treated or naive skin (P<.001 for both comparisons) [18].
• Our results also identify the keratinocyte as the cell of origin of the defect and suggest that this form of alopecia is due to absence of ligand-independent receptor function [12].
• In conclusion, heterozygosity for FHIT affects susceptibility of mice to spontaneous alopecia areata and B[a]P-induced preneoplastic lesions of the uterus and does not alter responsiveness to budesonide and NAC [21].
• Incontinentia pigmenti (IP) is an X-linked dominant disorder characterized by abnormal skin pigmentation, retinal detachment, anodontia, alopecia, nail dystrophy and central nervous system defects [22].
• Older mice develop mild alopecia and hyperplasia of sebaceous glands, particularly around the eyes [23].

Associations of Al with chemical compounds

• METHODS: After establishment of cyclophosphamide-induced alopecia, in either 3- or 7-week-old mice, AdShh or a control vector (AdNull) was delivered to dorsal skin by intradermal injection [18].
• To investigate whether the markedly elevated levels of 1,25-dihydroxyvitamin D led to the alopecia, we raised VDR-null mice in a ultraviolet light-free environment and fed them chow lacking vitamin D for five generations [12].
• Despite undetectable circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, alopecia persisted in the VDR-null mice, demonstrating that the alopecia was not secondary to toxic levels of 1,25-dihydroxyvitamin D interacting with an alternative receptor [12].
• Influence of FHIT on benzo[a]pyrene-induced tumors and alopecia in mice: chemoprevention by budesonide and N-acetylcysteine [21].
• Protection against doxorubicin-induced alopecia in rats by liposome-entrapped monoclonal antibodies [24].

Physical interactions of Al

• Transgenic mice overexpressing Hoxc13 in hair follicles (GC13 mice) exhibit complex phenotypic alterations including hair shaft defects and alopecia, as well as severe epidermal abnormalities [25].

Regulatory relationships of Al

• Alopecia and skin lesions were induced in CD200-deficient hosts by adoptive transfer of splenocytes from WT mice previously grafted with CD200-negative skin, but not from mice grafted with WT skin [26].
• Conditional epidermal expression of TGFbeta 1 blocks neonatal lethality but causes a reversible hyperplasia and alopecia [27].
• Overexpression of Bcl-2 protects from ultraviolet B-induced apoptosis but promotes hair follicle regression and chemotherapy-induced alopecia [28].
• In heparanase-overexpressing transgenic mice, increased levels of heparanase enhanced active hair growth and enabled faster hair recovery after chemotherapy-induced alopecia [29].
• Targeted expression of human vitamin d receptor in the skin promotes the initiation of the postnatal hair follicle cycle and rescues the alopecia in vitamin D receptor null mice [30].

Other interactions of Al

• We report that K17 null mice develop severe alopecia during the first week postbirth, correlating with hair fragility, alterations in follicular histology, and apoptosis in matrix cells [31].
• Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia [32].
• We show that transgenic mice overexpressing Hoxc13 in differentiating keratinocytes of hair follicles develop alopecia, accompanied by a progressive pathological skin condition that resembles ichthyosis [33].
• 'Cyclic alopecia' in Msx2 mutants: defects in hair cycling and hair shaft differentiation [34].
• The Smad4-mutant mice exhibited progressive alopecia as a result of the mutant hair follicles failing to undergo programmed regression [35].

Analytical, diagnostic and therapeutic context of Al

• Treatment of human scalp xenografts with antibodies to laminin-10, or its receptor beta1 integrin, produced alopecia [36].
• As compared with patients treated with chemotherapy alone, there was a significant decrease in the level of alopecia in patients receiving the combined therapy [37].
• Lymphocyte-mediated alopecia in C57BL/6 mice following successful immunotherapy for melanoma [38].
• To assess the ability of AS101 to protect against chemotherapy-induced alopecia, phase-II clinical trials have been initiated with cancer patients suffering from various malignancies [37].
• PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the degree of follicle damage and retarding the onset of cyclophosphamide-induced alopecia [39].

References