The <Emphasis Type="Italic">angora</Emphasis> gene weakens the effect of interaction of the mutant genes <Emphasis Type="Italic">wellhaarig</Emphasis> and <Emphasis Type="Italic">waved alopecia</Emphasis> in mice

The interaction of the mutant genes wellhaarig (we) and waved alopecia (wal) in mice was earlier demonstrated in our laboratory. The we gene significantly accelerates the appearance of alopecia in double we/wewal/wal homozygotes as compared to that in single +/+wal/wal homozygotes. It has been found in this work that the mutant gene angora-Y (Fgf5 ^go-Y ) weakens the effect of interaction of the we and wal genes. The first signs of alopecia appear in mice of the we/wewal/wal genotype at the age of 14 days, in triple Fgf5 ^go-Y /Fgf5 ^go-Y we/wewal/wal homozygotes alopecia is observed seven days later, i. e., in 21-day-old animals. The progression of alopecia in triple homozygotes is expressed to a lesser degree than in double +/+we/wewal/wal homozygotes. A single dose of the Fgf5 ^go-Y gene also decreases the effect of interaction of the we and wal genes, but less than a double dose of this gene. The first signs of alopecia in mice of the +/Fgf5 ^go-Y we/wewal/wal genotype appear only three days later than in double +/+we/wewal/wal homozygotes. The data obtained demonstrate that the Fgf5 ^go-Y gene is a powerful modifier of mutant genes determining the process of alopecia.     

Gene angora enhances the effects of gene waved alopecia in mice

Interaction between the mutant gene angora-Y (Fgf5(go-Y)) and the mutant gene waved alopecia (wal) in mice has been studied. Gene Fgf5(go-Y) in a homozygous state increases the length of hair of all types, whereas the homozygotes at wal gene display a waved hair with subsequent development of partial alopecia. Crosses between Fgf5(go-Y)/Fgf5(go-Y) and wal/wal mice gave the animals displaying the genotypes +/Fgf5(go-Y) wal/wal and Fgf5(go-Y)/Fgf5(go-Y) wal/walas well as F2 +/+ wal/wal mice. The first signs of alopecia in F2 +/+ wal/wal appear at the same time as in the mutant wal/wal BALB/c mice. This demonstrates that the genetic background has no effect on the expression of mutant gene wal. A single dose of gene Fgf5(go-Y) in +/Fgf5(go-Y) wal/wal mice causes a considerably earlier appearance of the first signs of alopecia compared with the +/+ wal/wal single homozygotes. The signs of alopecia in double homozygotes Fgf5(go-Y)/Fgf5(go-Y) wal/wal appear even earlier than in the mice +/Fgf5(go-Y) wal/wal. By the end of the first month after birth, the majority of double homozygotes have a virtually bold back with preserved scarce long hairs, guard hairs. Alopecia covers also the sides and belly. However, the head retains its hair and the regions of thinned long hairs remain on the limbs and near the tail base. The data obtained demonstrate that gene Fgf5(go-Y) is a modifier of gene wal, as it enhances considerably the effect of gene wal. This appears in an earlier development of alopecia and its more pronounced progress in the mice with genotypes +/Fgf5(go-Y) wal/wal and, particularly, Fgf5(go-Y)/Fgf5(go-Y) wal/wal.     

Interaction of mutant genes Fgf5go-Y, we, and wal changes the duration of hair growth cycles in mice

Mutant gene wallhaarig (wa) was acting as a modifier of the mutant gene waved alopecia (wal), substantially increasing hair loss rate in mice, as was previously shown in our laboratory. The current paper is devoted to a study of mutant gene angora-Y (Fgf5 ^go-Y ), which had extended anagen stage of the first and second generations hair growth cycles in triple heterozygotes (Fgf5 ^go-Y /Fgf5 ^go-Y we/we wal/wal). First generation guard hair in triple homozygotes had their anagen stage 4 days longer than the same stage in double homozygotes (+/+ we/we wal/wal). Hair loss started at a catagen stage in double homozygotes, while it started in triple homozygotes at the end of the same stage or even in a telogen. Such mutant gene interaction in hair follicle morphogenesis led to a partial recovery of a body hair coat in triple homozygotes.     

The we Gene is a Modifier of the walGene in Mice

Interaction of gene wellhaarig (we) with genes waved alopecia(wal) and hairless (hr) was studied in mice. The mutant gene weis responsible for the development of a specific waved coat in homozygotes. Homozygous mice carrying mutant gene walalso have a wavy coat, though a partial alopecia develops with time in these animals. In homozygotes for thehr gene, hair loss is observed beginning from the age of ten days. A series of crosses we/weand wal/wal yielded animals with we/+wal/wal and we/we wal/wal genotypes. In micewe/+wal/wal carrying gene we at a single dose, alopecia is accelerated significantly as compared to the single-dose homozygotes +/+wal/wal. In we/we wal/wal mice, alopecia starts earlier than in we/+wal/wal mice; by the age of one month, the double homozygotes are almost hairless except for small body areas covered with a sparse coat. In addition, curliness of the first-generation hair in mice we/we wal/wal is much more expressed than in +/+wal/wal and we/we+/+ mice. The obtained evidence suggests that the wegene is a modifier of the wal gene because the former enhances the effects of the walgene, which is confirmed by the earlier onset of alopecia and progression of the latter in mice having the we/+wal/wal genotype and especially in we/we wal/wal animals. The we/we hr/+ mice do not differ in coat from we/we+/+ mice; in both cases, the coat is wavy. The coat of double homozygotes we/we hr/hr, is similar to that of we/we+/+ mice until ten days of age, when the signs of alopecia appear. By the age of 21 days, mice we/we hr/hr have lost their coat completely like mice +/+ hr/hr. Hence, the we gene is a modifier of the walgene though it does not interact with hrgene during the coat formation.     

Gene <Emphasis Type="Italic">angora</Emphasis> as a modifier of the <Emphasis Type="Italic">hairless</Emphasis> gene in mouse

The interaction between mouse angora-Y (Fgf5 ^go-Y) and hairless (hr) genes have been studied. Homozygous mutant gene Fgf5 ^go-Y increases length of all hair types, while homozygotes for the h gene lose hair completely starting on day 14 after birth. We obtained mice with genotypes +/+ hr/hr F₂, +/Fgf5 ^go-Y hr/hr and Fgf5 ^go-Y/Fgf5 ^go-Y hr/hr. Both +/Fgf5 ^go-Y hr/hr and +/+ hr/hr mice began to loose hair from their heads on day 14. This further extended on the whole body. On day 21 the mice were completely deprived of hair. Therefore a single dose of gene Fgf5 ^go-Y does not modify alopecia in mice homozygous for hr. However in double homozygotes Fgf5 ^go-Y/Fgf5 ^go-Y hr/hr alopecia started 4 days later, namely on day 18. It usually finished 10–12 days after detection of first bald patches. On days 28–30 double homozygotes lose coat completely. Hair loss in double homozygous mice was 1.5-fold slower than in +/+ hr/hr mice. This resulted from a significant extension of anagen phase induced by a mutant homozygous gene Fgf5 ^go-Y in morphogenesis of the hair follicle. The hr gene was expressed at the transmission phase from anagen to catagen. Our data shows that the angora gene is a modifier of the hairless gene and this results in a strong repression of alopecia progression in double homozygous mice compared to +/+ hr/hr animals.     

The we gene is a modifier of the wal gene in mice

Interaction of gene wellhaarig (we) with genes waved alopecia (wal) and hairless (hr) was studied in mice. The mutant gene we is responsible for the development of a specific waved coat in homozygotes. Homozygous mice carrying mutant gene wal also have a wavy coat, though a partial alopecia develops with time in these animals. In homozygotes for the hr gene, hair loss is observed beginning from the age of ten days. A series of crosses we/we and wal/wal yielded animals with we/+wal/wal and we/we wal/wal genotypes. In mice we/+wal/wal carrying gene we at a single dose, alopecia is accelerated significantly as compared to the single-dose homozygotes +/+wal/wal. In we/we wal/wal mice, alopecia starts earlier than in we/+wal/wal mice; by the age of one month, the double homozygotes are almost hairless except for small body areas covered with a sparse coat. In addition, curliness of the first-generation hair in mice we/we wal/wal is much more expressed than in +/+wal/wal and we/we+/+ mice. The obtained evidence suggests that the we gene is a modifier of the wal gene because the former enhances the effects of the wal gene, which is confirmed by the earlier onset of alopecia and progression of the latter in mice having the we/+wal/wal genotype and especially in we/we wal/wal animals. The we/we hr/+ mice do not differ in coat from we/we+/+ mice; in both cases, the coat is wavy. The coat of double homozygotes we/we hr/hr, is similar to that of we/we+/+ mice until ten days of age, when the signs of alopecia appear. By the age of 21 days, mice we/we hr/hr have lost their coat completely like mice +/+ hr/hr. Hence, the we gene is a modifier of the wal gene though it does not interact with hr gene during the coat formation.     

Interaction of mutant genes Fgf5(go-Y), we, and wal changes the duration of hair growth cycles in mice

Mutant gene wallhaarig (wa) was acting as a modifier of the mutant gene waved alopecia (wal), substantially increasing hair loss rate in mice, as was previously shown in our laboratory. The current paper is devoted to a study of mutant gene angora- Y(Fgf5(go-Y)), which had extended anagen stage of the first and second generations hair growth cycles in triple heterozygotes (Fgf5(go-Y)/Fgf5(go-Y) we/we wal/wal). First generation guard hair in triple homozygotes had their anagen stage 4 days longer than the same stage in double homozygotes (+/+ we/we wal/wal). Hair loss started at a catagen stage in double homozygotes, while it started in triple homozygotes at the end of the same stage or even in a telogen. Such mutant gene interaction in hair follicle morphogenesis led to a partial recovery of a body hair coat in triple homozygotes.     

Gene angora as a modifier of the mouse hairless gene

The interactions between mouse angora-Y (Fgf5go-Y) and hairless (hr) genes have been studied. Homozygous mutant gene Fgf5go-Y increases hair length starting on day 14 after birth. We obtained mice with genotypes +/+ hr/hr F2, +/Fgf5go-Y hr/hr and Fgf5go-Y/Fgf5go-Y hr/hr. Both +/Fgf5go-Y hr/hr and +/+ hr/hr mice began to loose hair from their heads on day 14. This further extended on the whole body. On day 21 the mice were completely deprived of hair. Therefore a single dose of gene Fgf5go-Y does not affect alopecia mice homozygous for hr. However in double homozygotes Fgf5go-Y/Fgf5gO-hr/hr alopecia started 4 days later, namely on day 18. It usually finished 10-12 days after detection of first bald patches. On days 28-30 double homozygotes have lost all the hair. Hair loss in double homozygous mice was 1,5-fold slower than in +/+ hr/hr mice. This resulted from a significant extension of anagen phase induced by a mutant homozygous gene Fgf5go-Y in morphogenesis of the hair follicle. In contrast, hr gene was expressed only at the transmission phase from anagen to catagen. Our data shows that the angora gene is a modifier of the hairless gene and this results in a strong repression of alopecia progression in double homozygous mice compared to +/+ hr/hr animals.     

The mutant gene "wal" is active in cells of mouse hair follicles

In order to determine the place of action of the mutant gene waved alopecia (wal), we have obtained chimeric wal/wal c/c Gpi-1aa<-->+/+ C/C Gpi-1bb animals by aggregation of eight-cellular embryos of BALB/c-wal/wal mice and CBA (+/+) mice. The presence or absence of the chimeric structure was determined from the mosaic nature of fur color and hair structure, as well as on the basis of the presence of electrophoretically distinct variants of glucosephosphate isomerase in blood. Chimeras had alternating transverse patches of different lengths and widths consisting of curly (genotype wal/wal) or straight (genotype +/+) hairs. The percentage of cells with wal/wal mutant genotype in chimeras established on the basis of glucosephosphate isomerase isozymes varied from 10 to 80%. A higher percentage of the parental wal/wal component in chimeras correlated with the number of patches having wavy hairs. Analysis of the fur pattern represented by the alternation of transverse patches of wavy or straight hairs in chimeric wal/wal (+/+ mice has shown that mutant gene wal acts in ectodermal cells of hair follicles.     

The site of the action of the angora-Y gene and its interaction with the fuzzy-Y gene in the mouse

The site of action of the goY mutant gene was determined in the aggregation chimaeras C57BL-goY/goY----DBA (+/+). Chimerism was detected by mosaicism of coat pigmentation and electrophoretic pattern of glucose phosphate isomerase. In 28-day-old chimaeras the regions of light-brown coat alternated black coat, stripes of short hairs alternated those of long hairs. These stripes of different length and width extended from spine in lateral-ventral direction. The hairs plucked from long hairs stripes had a similar length that those of goY/goY mice of same age, but the hairs plucked from short hair stripes corresponded to the hair length of +/+ mice. These data show that the goY gene acts in epidermal cells of hair follicles and its expression is autonomous. It has been established that in double homozygotes goY/goYfzY/fzY both mutant genes are expressed: the considerable increase of hair length as compared to norm--the effect of the goY gene and curly coat--the effect of the fzY gene. In goY/goYfzY/fzY mice during the formation of G1 guard hairs the incomplete expression of the goY gene is observed that is due to the suppression of hair growth by the fzY mutant gene. The fzY gene does not suppress the growth of G2 hairs and therefore the full expression of the goY gene occurs in goY/goYfzY/fzY adult mice.     

Effects of the Mutant Gene wellhaarig in the Chimeric Mice

The mutant genewellhaarig(we) controls the formation of the waved coat in mice, which is most pronounced in homozygotes at 10 to 21 days of postnatal development. Abnormal hair growth and structure in the we/we mutant mice results from defective cell differentiation in the inner root sheath of a hair follicle. To localize the site of the we gene action, we obtained ten chimeric mice by aggregation of the early C57BL/6-2we/we and BALB/c embryos. The chimera coat was waved, shaggy, or almost normal depending on the percentage of the mutant component. In the we/we +/+ chimeric animals of the first generation (G1) aged 21 days, both mutant and normal hair phenotypes were observed, which was especially discernible in zigzag hair. Note that none of the chimeras exhibited the alternating patterns of transversely oriented stripes or patches of either mutant or normal hair; i.e., they had a mixed parental hair phenotype. We also did not observe the animals with an intermediate phenotype, which suggests a discontinuous hair formation in chimeras according to the all or nothing principle. The data obtained indicate that the dermal papilla cells of a hair follicle are the sites for the we gene action. During the embryonic development, dermal cells are strongly mixed, which accounts for the lack of the clear-cut transverse stripes of either mutant or normal hair. The mutant genewe is probably responsible for a disrupted induction signal from the dermal papilla towards ectodermal cells of a hair follicle.     

Effects of the mutant gene wellhaarig in chimeric mice

The mutant gene wellhaaring (we) confers the waved coat in mice, which is most pronounced in homozygotes at 10 to 21 days of postnatal development. Abnormal hair growth and structure in the we/we mutant mice results from defective cell differentiation in the inner root sheath of a hair follicle. To localize the site of the we gene action, we obtained ten chimeric mice by aggregation of the early C57BL/6-2we/we and BALB/c embryos. The chimera coat was waved, shaggy, or almost normal depending on the percentage of the mutant component. In the we/we +/+ chimeric animals of the first generation (G1) aged 21 days, both mutant and normal hair phenotypes were observed, which was especially discernible in zigzag hair. Note that none of the chimeras exhibited the alternating patterns of transversely oriented stripes or patches of either mutant or normal hair; i.e., they had a mixed parental hair phenotype. We also did not observe the animals with an intermediate phenotype, which suggests a discontinuous hair formation in chimeras according to the "all or nothing" principle. The data obtained indicate that the dermal papilla cells of a hair follicle are the sites for the we gene action. During the embryonic development, dermal cells are strongly mixed, which accounts for the lack of the clear-cut transverse stripes of either mutant or normal hair. The mutant gene we is probably responsible for a disrupted induction signal from the dermal papilla towards ectodermal cells of a hair follicle.     

Depilated (dep), a Mutant Gene That Affects the Coat of the Mouse and Acts in the Epidermis

Depilated is a recessive mutation on Chromosome 4 in the position b^-1.93±0.51^- dep^-3.45±0.68.^-Pt. It causes severe abnormalities of hair structure. The site of action of dep was investigated by the method of dermal-epidermal recombination. Skins from 14-day mutant and normal mouse embryos were separated into dermal and epidermal components, recombined, and grown in histocompatible mouse testes for 20 days. The recombinations made were +/+ epidermis with +/+ dermis, +/+ epidermis with dep/dep dermis, dep/dep epidermis with +/+ dermis and dep/dep epidermis with dep/dep dermis. Grafts that contained mutant epidermis as one of the components produced hairs that were similar to those found in depilated mice. There was no observable effect of the dermis on hair types produced in this experiment.     

In vivo and in vitro comparison of the effects of FGF-2 null and haplo-insufficiency on bone formation in mice

We previously reported that deletion of the Fgf2 gene (Fgf2-/-) resulted in decreased bone mass in adult mice. This study examines the effect of haplo-insuffiency (Fgf2+/-) on bone loss in vertebrae from these mutant mice. Fgf2+/+ mice attained peak bone mass at 8-9 months of age. In contrast BMD was significantly reduced in vertebrae from adult (8-9) Fgf2+/- mice. Exogenous FGF-2 rescued reduced bone nodule formation in Fgf2+/- and Fgf2-/- cultures. Runx2 mRNA was reduced in cultures from Fgf2+/- and Fgf2-/- mice. FGF receptor2 mRNA and protein were markedly reduced in Fgf2+/- and Fgf2-/- mice. Decreased bone formation in Fgf2 mutant mice may correlate with impaired FGFR signaling, decreased Runx2 gene expression.     

The mutant gene wellhaarig disturbs the differentiation of hair follicle cells in the mouse]

First generation (G1) hairs in mice homozygous for the wellhaarig (we) gene are wavy and shorter than in normal mice; basal regions of the hairs are deformed. Follicles of G1 hairs in mid-dorsal region of 8-, 12- and 16-days old we/we mice were examined. Huxley cells of the inner root sheath (IRS) in apical region of hair follicles appeared to be hypertrophied. Cytoplasm of these cells was not stained by basic dyes and showed no birefringence. Cytoplasm of the IRS Henle cells was not stained by basic dyes either. These data indicate that keratinization of the IRS cells is disturbed in mutant homozygotes. The layer of outer root sheath in the we/we mice was thinner than in normal mice; this is probably due to hypertrophy of the IRS cells. The structure of differentiating cells of the hair shaft in normal and mutant mice was similar. The data obtained suggest that abnormal G1 hairs in we/we mice result from disturbance in IRS cells differentiation.     

The Effects of Mutant Gene hairless in Chimeric Mice

The autosomal recessive gene hairless (hr) is responsible for the complete hairlessness in mice homozygous for this gene. Hair shedding that begins at the age of 10 days is caused by an abnormal cycle of hair follicle development disturbed at the catagen stage. This results in enhanced programmed cell death (apoptosis) and ultimately leads to the complete hair follicle destruction and shedding of all hairs by the age of three weeks. To study the phenotypic expression of the hr gene in a chimeric organism, we have obtained 12 chimeric mice hr/hr +/+ by means of aggregation of early embryos hr/hr and +/+. In chimeric mice, the hair shedding has begun two days later than in the hr/hr mice. By day 23 of postnatal development, hairless areas were present on the coat of chimeric mice or the latter were completely hairless depending on the percentage of the hr/hr mutant component. In four chimeras with high content of the mutant component (68–76%), the hair shedding process was similar to that in the hr/hr mice, though it was accomplished two days later. In three chimeras with 48–51% of the mutant component, alternating hairless and hair-covered bands were observed. These data suggest that the hr gene acts in epidermal cells of a hair follicle, because epidermal cell clones in embryonic skin migrate in the lateral–ventral direction coherently and without mixing. However, some chimeras displayed a pattern which was not so clear-cut: the band borders were illegible and hairs partly covered the hairless areas. In some chimeras, the uniform thinning of the coat was observed. Analysis of the effects of the hr mutant gene in chimeric mice differing in the ratio between mutant (hr/hr) and normal (+/+) components in tissues suggests that the hrgene acts in the epidermal cells of the hair follicle. The interactions between cells have an essential effect on the mode and degree of the hr gene expression, which leads to distortion of the ectodermal coat pattern in chimeras.     

Analysis of the effects of mutant hairless genes in chimeric mice

The autosomal recessive gene hairless (hr) is responsible for the complete hairlessness in mice homozygous for this gene. Hair shedding that begins at the age of 10 days is caused by an abnormal cycle of hair follicle development disturbed at the catagen stage. This results in enhanced programmed cell death (apoptosis) and ultimately leads to the complete hair follicle destruction and shedding of all hairs by the age of three weeks. To study the phenotypic expression of the hr gene in a chimeric organism, we have obtained 12 chimeric mice hr/hr <--> +/+ by means of aggregation of early embryos hr/hr and +/+. In chimeric mice, the hair shedding has begun two days later than in the hr/hr mice. By day 23 of postnatal development, hairless areas were present on the coat of chimeric mice or the latter were completely hairless depending on the percentage of the hr/hr mutant component. In four chimeras with high content of the mutant component (68-76%), the hair shedding process was similar to that in the hr/hr mice, though it was accomplished two days later. In three chimeras with 48-51% of the mutant component, alternating hairless and hair-covered bands were observed. These data suggest that the hr gene acts in epidermal cells of a hair follicle, because epidermal cell clones in embryonic skin migrate in the lateral-ventral direction coherently and without mixing. However, some chimeras displayed a pattern which was not so clear-cut: the band borders were illegible and hairs partly covered the hairless areas. In some chimeras, the uniform thinning of the coat was observed. Analysis of the effects of the hr mutant gene in chimeric mice differing in the ratio between mutant (hr/hr) and normal (+/+) components in tissues suggests that the hr gene acts in the epidermal cells of the hair follicle. The interactions between cells have an essential effect on the mode and degree of the hr gene expression, which leads to distortion of the "ectodermal" coat pattern in chimeras.     

Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice

Since parathyroid hormone (PTH) increased FGF2 mRNA and protein expression in osteoblasts, and serum FGF-2 was increased in osteoporotic patients treated with PTH, we assessed whether the anabolic effect of PTH was impaired in Fgf2-/- mice. Eight-week-old Fgf2+/+ and Fgf2-/- male mice were treated with rhPTH 1-34 (80mug/kg) for 4 weeks. Micro-CT and histomorphometry demonstrated that PTH significantly increased parameters of bone formation in femurs from Fgf2+/+ mice but the changes were smaller and not significant in Fgf2-/- mice. IGF-1 was significantly reduced in serum from PTH-treated Fgf2-/- mice. DEXA analysis of femurs from Fgf2+/+, Fgf2+/-, and Fgf2-/- mice treated with rhPTH (160mug/kg) for 10 days showed that PTH significantly increased femoral BMD in Fgf2+/+ by 18%; by only 3% in Fgf2+/- mice and reduced by 3% in Fgf2-/- mice. We conclude that endogenous Fgf2 is important for maximum bone anabolic effect of PTH in mice.     

ALK5-Mediated Transforming Growth Factor β Signaling in Neural Crest Cells Controls Craniofacial Muscle Development via Tissue-Tissue Interactions

The development of the craniofacial muscles requires reciprocal interactions with surrounding craniofacial tissues that originate from cranial neural crest cells (CNCCs). However, the molecular mechanism involved in the tissue-tissue interactions between CNCCs and muscle progenitors during craniofacial muscle development is largely unknown. In the current study, we address how CNCCs regulate the development of the tongue and other craniofacial muscles using Wnt1-Cre; Alk5^fl/fl mice, in which loss of Alk5 in CNCCs results in severely disrupted muscle formation. We found that Bmp4 is responsible for reduced proliferation of the myogenic progenitor cells in Wnt1-Cre; Alk5^fl/fl mice during early myogenesis. In addition, Fgf4 and Fgf6 ligands were reduced in Wnt1-Cre; Alk5^fl/fl mice and are critical for differentiation of the myogenic cells. Addition of Bmp4 or Fgf ligands rescues the proliferation and differentiation defects in the craniofacial muscles of Alk5 mutant mice in vitro. Taken together, our results indicate that CNCCs play critical roles in controlling craniofacial myogenic proliferation and differentiation through tissue-tissue interactions.     

An analysis of the expression of the mutant angora-Y gene in the mouse

We studied the rate and duration of the growth of G1 and G3 hairs in mice homozygous for angora-Y mutant gene (goY). The follicular diameter of G3 hairs and the growth rate of G1 and G3 hairs in goY/goY mice do not differ from normal. However, the duration of growth period of all four studied types of hairs in goY/goY mice is longer than in the normal phenotype. Growth of the guard hairs G1 and G3 in mutants continues longer than in the normal phenotype by 7 and 3 days, respectively. For other hair types G1 and G3 (awl, auchene, zigzag) the duration of the growth period is approximately 3 days longer than in the control. As a result in goY/goY mice guard hairs G1 and G3 which have completed growth are 2 and 1.5 times longer than in +/+ mice. Other types of G1 hairs in mutants are longer by 50% and G3 hairs by 30% than in the wild type.