Increased Vibrissa Growth in Transgenic Mice Expressing Insulin-like Growth Factor 1

Abstract

Insulin-like growth factor 1 (IGF-1) mediates many of the actions of growth hormone. Overexpression of IGF-1 has been reported to have endocrine and paracrine/autocrine effects on somatic growth in transgenic mice. To study the paracrine/autocrine effects of IGF-1 in hair follicles, transgenic mice were produced by pronuclear microinjection of a construct containing a mouse ultra-high sulfur keratin (UHS-KER) promoter linked to an ovine IGF-1 cDNA. This UHS-KER promoter has previously been shown to direct expression of a reporter gene to the hair follicles of transgenic mice. Four transgenic mouse lines were established as a result of microinjection of 435 embryos. Transgene expression was found in skin at day 8 and day 15 of age in three of the lines. Progeny tests were carried out by mating two of the transgenic expressing males to nontransgenic females. Mice from one line were all nonexpressors while four of the 12 mice from the other showed integration of the transgene and three expressed transgene IGF-1 mRNA in the skin. Vibrissa growth at 11-21 d of age was significantly greater in transgenic expressors than in their nontransgenic littermates. Specifically, the increase in vibrissa length for transgenics at days 11-16 (20.5%) is approximately 2-fold compared with days 16-21 (11.9%). These results demonstrate that local overexpression of IGF-1 in transgenic mice is capable of stimulating vibrissa growth during the first neonatal hair cycle.

Overexpression of mIGF-1 in Keratinocytes Improves Wound Healing and Accelerates Hair Follicle Formation and Cycling in Mice

“…As expected, these alterations result in elongation of the guard and awl hair shafts in the skin of K14/mIGF-1 transgenic mice. In the previous in vivo studies, additional IGF-1 was supplied by differentiated noncycling cells of the hair follicle, 25,26 and the suggested mechanism of growth enhancement involved either stimulation of the follicular metabolism, or the ability of IGF-1 to diffuse into the follicular bulb and to stimulate proliferation of the actively cycling matrix cells. Transgenic mice overexpressing IGF-1 under a keratin 1 promoter showed earlier hair appearance, 8 and this effect is also likely to involve IGF-1 diffusion or activation of other cell types in the skin.…”

“…24 Transgenic animals, in which an ultra-highsulfur keratin gene promoter was used to target IGF-1 to the wool follicles of the sheep or hair follicles of the mouse, showed increased fleece weight and vibrissae length, respectively. 25,26 Hair appeared earlier in transgenic mice overexpressing IGF-1 in the skin under control of the keratin 1 (K1) promoter. 8 In contrast, hair follicles of transgenic mice expressing IGF-1 in the skin under control of the involucrin promoter, showed a delay in anagen entry.…”

Segmental Igfbp5 expression is specifically associated with the bent structure of zigzag hairs

“…Although IGF-I takes part in differentiation processes, its mitogenic activity appears to be the most prominent function (Hsieh et al, 2004;Musaro and Rosenthal, 1999;Stewart and Rotwein, 1996). In skin, this interpretation is supported by the hyperproliferation of Igf-I-positive epidermis and the increased length of Igf-I expressing whiskers in transgenic mouse models (Bol et al, 1997;Su et al, 1999). IGF-I may also have an influence on the progression of the hair cycle, since medium lacking IGF-I causes in vitro cultured hair follicles to enter a regression-like state (Philpott et al, 1994).…”

“…Withdrawal of IGF-I from the medium induced a transformation reminiscent of the regression phase of the hair cycle which is characterised by a stop of proliferation in the epithelial compartment (Philpott et al, 1994;Tezuka et al, 1990). On the contrary, transgenic expression of Igf-I in the interfollicular epidermis causes epidermal hyperplasia, whereas ectopic expression in the hair follicle stimulates vibrissa growth (Bol et al, 1997;Su et al, 1999). Mice deficient for either Igf-I or Igf-II show no apparent epidermis or hair follicle phenotype (DeChiara et al, 1990;Liu et al, 1993).…”

Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes

“…Conversely, ectopic expression of Igf1 promotes hair growth and follicular elongation (Su et al, 1999a;Su et al, 1999b;Weger and Schlake, 2005a). Importantly, mice overexpressing both Igf1 and Igfbp3 are normal (Weger and Schlake, 2005a), indicating that IGF/Igfbp3 balance is an important regulator of follicular keratinocyte proliferation.…”