Biomedical subjects

B V Koniukhov

Publications and source records attributed to B V Koniukhov.

At least 19 recordsLinked to original sources

PubMed2004

[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.

Animals↗

PubMed2003

[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.

Animals↗

PubMed2002

[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.

Animals↗

PubMed2001

[Genomic imprinting in mammals].

A review of the data on the mechanisms and effects of genomic imprinting, an epigenetic phenomenon regulating the development in placentate mammals, is presented. In contrast to the majority of gene loci with biallelic expression, the expression of imprinted loci is monoallelic. In humans and mice, more than 300 imprinted loci have been identified, in which maternal or paternal alleles may either be expressed or be found in a repressed state during ontogeny. Imprinting is established during gametogenesis, and the repression of an allele of the imprinted locus is determined by methylation of the key regulatory element of this allele. Both the maternal and paternal chromosome sets are required for normal development in mammals. This is why parthenogenesis and androgenesis in these animals are impossible in nature. As a result of differential gene expression of many imprinted loci, the balance of gene activity is established, which is necessary for normal proliferation and differentiation of various cell clones in embryogenesis. Many human developmental abnormalities and syndromes are determined by defective genomic imprinting. In particular, the loss of imprints, which is followed by the occurrence of biallelic expression of some imprinted loci, may cause malignant tumors.

Alleles↗

PubMed2001

[Transforming growth factor alpha (TGFalpha) modulates the effect of genomic imprinting and prolongs the development of parthenogenetic murine embryos].

The effect of transforming growth factor alpha (TGF alpha) on the development of diploid parthenogenetic mouse embryos (CBA x C57BL/6)F1 was studied. The embryos were in vitro treated with the TGF alpha at the stage of morula. Upon reaching the blastocyst stage, each embryo was implanted into uterus of a pseudopregnant female. At a dose of 5 ng/ml, the TGF alpha was found to improve development of parthenogenetic embryos before implantation, increase significantly the number of developing blastocysts, and promote embryo implantation into uterus. After treatment with TGF alpha at a dose of 10 ng/ml, 4% of parthenogenetic embryos reached the stage of 30-45 somites and had forelimb and hindlimb buds; the embryo size from vertex to sacrum was 2.0 to 3.8 mm. A well-developed placenta was observed in 6% of TGF alpha-treated parthenogenetic embryos that reached the somite stages. In the parthenogenetic embryos with the most prominent development (42-45 somites) treated with 10 ng/ml of TGF alpha, the placental diameter was 4.0 to 4.2 mm on day 12 of gestation, which is close to the placental size of the normal (fertilized) 11-day-old mouse embryos. Our results suggest that endogenous TGF alpha can modulate the effects of genomic imprinting significantly improving formation of trophoblast derivatives and promoting longer postimplantation development of parthenogenetic embryos.

Animals↗

PubMed1997

[Cloning of vertebrates: successes and problems].

Cloning of vertebrates, in particular, amphibians and mammals, is discussed. In the last decade, significant progress was made cloning mammals, while cloning of adult amphibians remained problematical. Low-traumatic methods of enucleation of recipient oocytes and transplantation of donor nuclei were worked out. In 1997, an adult sheep was cloned in Great Britain, thus demonstrating the possibility of cloning adult mammals. However, methods of cloning mammals need improvement because of the high lethality of reconstructed embryos (nuclear transplants). The use of in vitro cultured low-differentiated stem cells to obtain donor nuclei seems promising. Works on human cloning are not expedient in the near future because of technical and ethical aspects.

Animals↗

PubMed1996

[Expression of the mutant gene mi in mice: white spotting pattern].

Mice of mi/+ and +/+ genotypes of the mutant stock microphthalmia (mi) were mated inter se and with those of CC57BR/Mv and CBA/J inbred lines. In all types of crosses, the offsprings of mi/+ genotype had unpigmented fingers and distal tail parts (penetrance 100%). This trait is determined mostly by the mutant mi gene, the expression of which is not affected by modifier genes. However, the degree of mi gene expression, white spotting, on other body parts (wrist, foot, ventral body side, and parietal head part) varied widely in mice obtained from different crosses; penetrance ranged from 0 to 100%. The results obtained indicate that in these cases, the expression of mi gene was strongly affected by modifier genes. The different frequency of the mi gene effects, in heterozygote offspring obtained from reciprocal crosses, can result from the imprinting of the modifier genes in maternal and paternal gametes.

Animals↗

PubMed1988

[Chimeric drift in blood erythrocyte population in BALB/c----C57BL/10 and BALB----B10.D2 mice].

Genotypic composition of the erythrocyte population of peripheral blood in 16 aggregation chimeras: BALB/c (H-2dd)----C57BL/10(H-2bb) and BALB/c(H-2dd)----B10.D2(H-2dd) was studied during 10 months. The proportion of cells of parental components was defined visually in the coat and by electrophoresis of allozyme variants at the Gpi-1 locus in blood. The similar increase of blood cells percentage was observed in blood of both types of chimeras with age. In chimeras the skin grafts of both parental types survive. Chimeric drift is not caused by H-2 haplotypes differences between cells of two strains or disturbance of immunological tolerance in the chimeric mice. We propose that chimeric drift results from interaction of hemopoietic cells of different strains in early stages of hemopoiesis.

Animals↗

PubMed1987

[The genetics of animal development].

The stages of establishment of phenogenetics in the USSR are regarded in this paper. The major directions and schools in this field are described. Also, main achievements and conceptions developed by our phenogeneticists are analysed in detail.

Animals↗

PubMed1986

[Expression of mutant eyeless genes in the mouse embryo retina].

The aim of the present study was to determine the cellular site of eyeless-I (ey-I) and eyeless-2 (ey-2) gene action, causing anophthalmia or microphthalmia. Eye primordia from 10-day-old embryos of ZRDCT-AN and CC57BR (control) mice were cultured in vitro for 3 or 6 days. In 59 out of 77 cultured mutant eye primordia neural retina was disturbed. In 9 mutant eye primordia the disturbed neural retina was 4-6 times thinner than in the control. However, lens differentiation was similar to that in the control, epithelial and fibrous components were observed. Thus, mutant genes eyeless inhibit the growth of primordial retina, causing secondary developmental defects of the lens and other eye structures.

Animals↗

PubMed1982

[Interaction of the mutant aphakia, fidget and ocular retardation genes in mice].

The phenogenetic analysis of the effects of aphakia (ak) gene and its interaction with the ocular retardation (or) and fidget (fi) genes suggests that the ak gene acts in the lens cells with the result of arresting lens fibre differentiation. In mice homozygous for ak, the lens failure leads to secondary retina defects, in particular, to formation of retinal folds. In ak/ak or/or mice, the lens and retina morphogenesis stops at the optic cup stage, the eye is strongly reduced in size and more affected, compared to the corresponding single homozygotes. Unlike ak/ak or/or, in the ak/ak fi/fi mice the eyes are more regular in shape than those in the ak/ak +/+ condition. The fi gene inhibition of the retina anlage growth leads to some improvement of the eye development in double ak/ak fi/fi homozygotes, due to the absence of extensive retina folding.

Animals↗

PubMed1981

[Gamma- and beta-crystallin gene activation during lens morphogenesis in mice].

Lens anlages from 10-day-old mouse embryos exposed to the treatment with actinomycin D during one hour were cultivated for 15, 18 or 20 hours. Expression of gamma- and beta-crystalline genes was studied by the indirect immunofluorescence technique. It is shown that the activation of gamma- and beta-crystalline genes took place in the first stages of the formation of lens fibers, when the cells of the proximal wall of the lens vesicle were undergoing the last mitotic cycle.

Animals↗

PubMed1981

[Phenogenetic analysis of recessive epistasis of the or gene over the Bld gene in mice].

Results concerning interaction between the genes blind (Bld) and ocular retardation (or) during mouse embryogenesis are presented. It was established that in Bld/+ or/or mice the Bld gene effects are not expressed, as a result of the pronounced eye reduction caused by the or gene action. In Bld/+ or/or embryos the phenocritic stage of the Bld gene action is deplaced to more early embryogenesis period than that in the Bld/+ +/+ embryos. This leads to the recessive epistasis of the or gene over the Bld gene. The analysis of gene interaction has also indicated that the lid mesodermal component growth is the primary target process affected by the Bld/+ constitution.

Animals↗

PubMed1981

[Effects of a single dose of the mutant gene CatFr in mouse ontogeny].

A study of the lenses of CatFr/+ and +/+ mice at different stages of embryonic and postembryonic development by means of electron and light microscopy has shown that the effect of CatFr gene single dose is characterized by a more rapid denucleation of lens fibers, as compared with the normal development. Defects of the nuclear envelope structure, similar with those described earlier for homozygotes, were observed in the developing lenses of heterozygotes. In CatFr/+ mice, unlike in homozygotes, the nuclei of primary lens fibers are not practically affected but those of secondary fibers are destroyed, thus leading to the lysis of these fibers and the development of cataract. The expression of CatFr gene in heterozygotes is due to additive interaction of its effects and "denucleation" process.

Animals↗

PubMed1981

[Action of mutant genes on crystallin synthesis in the developing mouse lens. III. The aphakia gene].

The synthesis of crystallins was studied by means of indirect immunofluorescence in 10-18 days old embryos and newborn ak/ak mice. Immune gamma-globulins to alpha-, beta- and gamma-crystallins of adult mice were used. A small amount of alpha-crystallins was found in an abnormal lens vesicle of 14 days old ak/ak embryo. The initiation of synthesis of these proteins is, hence, delayed by 4 days, as compared with that in the normal mice. In 15 days old mutant embryos the amount of alpha-crystallins increased markedly and was kept at about the same level till the end of embryogenesis. In the newborn ak/ak mice, the lens material containing alpha-crystallins is distributed among the retinal folds and is not readily identified without immunofluorescence. No lens material was found in the adult mutant mice. gamma- and beta-crystallins were not found in the abnormal lens at all developmental stages studied.

Animals↗

PubMed1978

[Site of fidget gene action and its interaction with the ocular retardation gene in cultured mouse embryo retinas].

The eye rudiments of 10 and 11 days old mouse embryos of the genotypes +/+ +/+, fi/fi +/+, +/+ or/or, fi/fi or/or and 11 days old embryos of the genotype fi/+ or/+ were cultivated in vitro during 24, 48 and 72 hrs. The expression of the fi gene was shown in the cells of the cultivated fi/fi +/+ retina: its proliferative activity was inhibited. The fi gene was not active in the cells of the developing lens and the anomalies of the latter in homozygotes arose secondarily, due to the inhibition of growth of the retinal rudiment. The fi and or genes interacted synergically in the cultivated fi/fi or/or retina, thus resulting in the marked inhibition of its mitotic activity. This suggests that both the genes act in the retinal cells and, apparently, affect different links of the biochemical chain of events in the preparation of DNA replication.

Animals↗

PubMed1978

[Regulator of expression of the brachypodism-H gene in mice].

Extracts were prepared from the whole limb buds of the 11 day-old mouse embryos and from the postaxial or preaxial parts of the 12 day-old embryo limb buds. Effects of these extracts on the growth of the 13 day-old bpH/bpH embryo tibia rudiments were studied in vitro. It was shown that the limb buds of the 11- and 12 day-old mouse embryos contain a factor regulating bpH gene expression in differentiating cartilage cells. This factor is present in the postaxial part of the limb bud and is absent in its preaxial one. When the extract from the limb bud postaxial parts of the 12 day-old +/+ embryos is added to culture medium, the expression of bpH gene is observed in cultured tibia rudiments of the 13 day-old bpH/bpH embryos. The extraxt from the limb bud preaxial parts of the 12 day-old +/+ embryos does not affect the growth of tibia rudiments of mutant embryos in vitro. The regulator factor does not induce bpH gene expression in cultured bone rudiments of the 14 day-old bpH/bpH embryos. It is obvious that bpH locus does not act in cartilage cells of developing tibia after the 14th day of embryogenesis. The sensitivity of the factor regulating bpH gene expression to heating and proteolytic enzymes suggests its protein nature. The molecular weight of this protein is from 15 000 to 25 000. Experiments with actinomycin D show that this factor regulates the expression of bpH at the post-transcriptional level.

Achondroplasia↗

PubMed1977

[Influence of mutant genes on crystallin synthesis in the forming mouse lens. II. Fidget and ocular retardation genes].

The beginning of synthesis and the localization of alpha- and gamma-crystallins in the developing lenses of the 10-13 and 15 days old mouse embryos of the genotypes fi/fi +/+, +/+ or/or, fi/fi or/or and +/+ +/+ were studied by means of indirect immunofluorescence. The synthesis of crystallins in the mutant embryos with the exception of the embryo +/+ or/or was shown to begin somewhat later than in the normal ones but to proceed in all defective lenses, irrespective of the degree of defect. Hence, the activation of the genes controlling the synthesis of alpha-crystallins begins at the early stages of lens development and the synthesis of these proteins proceeds even during the abnormal with the slowing down of the formation of primary lens fibers. In the cases of strong defects of morphogenesis in the fi/fi +/+ and, especially, fi/fi or/or, embryos gamma-crystallins were not detected. The synthesis of gamma-crystallins appears to begin at the final stages of lens fiber differentiation.

Animals↗