Platinum coat color in red fox (Vulpes vulpes) is caused by a mutation in an autosomal copy of KIT.

The red fox (Vulpes vulpes) demonstrates a variety of coat colors including platinum, a common phenotype maintained in farm-bred fox populations. Foxes heterozygous for the platinum allele have a light silver coat and extensive white spotting, whereas homozygosity is embryonic lethal. Two KIT transcripts were identified in skin cDNA from platinum foxes. The long transcript was identical to the KIT transcript of silver foxes, whereas the short transcript, which lacks exon 17, was specific to platinum. The KIT gene has several copies in the fox genome: an autosomal copy on chromosome 2 and additional copies on the B chromosomes. To identify the platinum-specific KIT sequence, the genomes of one platinum and one silver fox were sequenced. A single nucleotide polymorphism (SNP) was identified at the first nucleotide of KIT intron 17 in the platinum fox. In platinum foxes, the A allele of the SNP disrupts the donor splice site and causes exon 17, which is part of a segment that encodes a conserved tyrosine kinase domain, to be skipped. Complete cosegregation of the A allele with the platinum phenotype was confirmed by linkage mapping (LOD 25.59). All genotyped farm-bred platinum foxes from Russia and the US were heterozygous for the SNP (A/G), whereas foxes with different coat colors were homozygous for the G allele. Identification of the platinum mutation suggests that other fox white-spotting phenotypes, which are allelic to platinum, would also be caused by mutations in the KIT gene.

[The effects of prolonged selection for behavior on the stress response and Activity of the reproductive system of male Brown rats (Rattus norvegicus)].

Two Norway rat (Rattus norvegicus) populations contrasting in behavior have been raised at the Institute of Cytology and Genetics, Novosibirsk, Russia with long-term selection for the absence or enhancement of an aggressive response towards humans. They are designated as tame and aggressive, respectively. In this work we investigated the effects of the selection on behavior, stress responsiveness, and fertility in males of the 78th generation. It is shown that the difference between the strains in their response to humans remains the same as in previous generations. However, the differences in stress response and maturation age contradict earlier data. For the first time, we note a higher glucocorticoid-mediated response to restriction stress and retarded sexual maturation in tame rats compared to aggressive ones, according to morphometric indices of gonads and testosterone levels. It is conceivable that the change in selection effects is determined by the disjunction of the directions of selection for behavior and the modification of the stress response. This study is the first to characterize males recently (six or seven generations of propagation in captivity) caught in the wild with regard to the indices under consideration and used as a control group. Wild rats have the highest stress response and rate of sexual maturation as compared to those selected.

The expression profile of genes associated with behavior, stress, and adult neurogenesis along the hippocampal dorsoventral axis in tame and aggressive foxes.

The hippocampus plays the key role in stress response regulation, and stress response appears to be weakened in domesticated animals compared to their wild relatives. The hippocampus is functionally heterogeneous along its dorsoventral axis, with its ventral compartment being more closely involved in stress regulation. An earlier series of experiments was conducted with a unique breeding model of animal domestication, the farm silver fox (Vulpes vulpes), which included tame, aggressive, and unselected animals. A decrease in many indices of the hypothalamic-pituitary-adrenal activity was observed in tame animals. Also, adult hippocampal neurogenesis was more intense in tame foxes, and this fact may relate to reduced stress levels in this experimental population of foxes. Nevertheless, the molecular mechanisms responsible for the reduced stress response in tame animals remain obscure. In this study, serum cortisol levels and the mRNA levels of 13 genes in the dorsal and ventral hippocampus have been measured and compared in tame, aggressive, and unselected foxes. At the current stage of domestication, stress-induced cortisol levels in tame, aggressive, and unselected animals differ significantly from each other: tame foxes show the lowest levels, and aggressive ones, the highest. Twelve genes tested demonstrate significant gene expression differences between the dorsal and ventral hippocampi. These differences are mainly consistent with those found in rodents and humans. In tame foxes, significantly elevated mRNA levels were recorded for several genes: CYP26B1 for cytochrome P450 26B1 and ADRA1A for α1A adrenergic receptor in the dorsal hippocampus, whereas the level of NR3C2 mRNA for mineralocorticoid receptor was higher in the ventral. It is presumed that these genes constitute an important part of the mechanism reducing stress induced by contacts with humans and contribute to linking stress regulation with adult neurogenesis in tame foxes and domesticated animals in general.

[Effects of maternal methyl-supplemented diet on glucocorticoid receptor gene expression in the hippocampal of rats selected for behavior].

Here we report that selection for behavior and maternal methyl-supplemented diet alters rat hippocampus glucocorticoid receptor (GR) mRNA expression. Same selection is associated with increased GR mRNA expression as compared with aggressive rats, whereas maternal methyl-supplemented diet inhibits tame rat GR gene activity. The gene promoter methylation is a way to alter GR expression.

Adolescent oxytocin treatment affects resident behavior in aggressive but not tame adult rats.

There are indications that exposing adolescent rodents to oxytocin (OT) promotes social activity and reduces anxiety in adulthood. Adult male gray rats selected for elimination and enhancement of the aggressive response to humans, when exposed to OT, showed divergent changes in the resident behavior towards the intruder. It could be assumed that adolescent administration of both OT and antagonist of OT receptor (OTR) would also have different long-term effects on resident behavior and startle reflex in adult aggressive and tame rats. The aim of this work is to study the long-term effects of adolescent administration of both OT and antagonist of OT receptor (OTR) on resident behavior and startle reflex in adult tame and aggressive male gray rats. Starting at the age of 28 days, the animals received nasal applications of 5 µL of oxytocin solution (1 µg / µL) or saline for 5 days (daily). At the age of two months, the acoustic startle amplitude was assessed in two series of 5 acoustic stimuli. The resident-intruder test was performed one week later. Antagonist of OT receptor l-368,899 was administered intraperitoneally (i.p.) once at a dose of 5 mg/kg at the age of 30-33 days. Subsequent startle reflex tests were performed 20 days later, at the age of 50-53 days. A week later, the resident-intruder test was performed on the same rats. The startle amplitude in aggressive rats of the control group (in two series of acoustic stimuli) and those having received saline (in the first series) was larger than in the corresponding tame groups. Oxytocin and saline solutions did not significantly affect the startle amplitude compared to control animals. After saline administration, the attack latency in tame rats was longer than in aggressive rats (P <0.05). Oxytocin treatment caused a prolongation of this period in aggressive males compared with control animals receiving saline solution (P <0.01). In addition, oxytocin administration in aggressive males caused an increase in the time of social behavior, which did not include aggressive and same-sex behavior, as compared with the corresponding control animals (P <0.05). Exogenous oxytocin receptor antagonist (l-368,899) did not affect the startle amplitude and behavior in the resident-intruder test in aggressive and tame male rats. Adolescent OT treatment causes a prolongation of both the attack latency and social behavior in the resident-intruder test in adult aggressive male rats, but does not affect these parameters in tame rats.

[The effect of methyl-containing supplements during pregnancy on the phenotypic modification of offspring hair color in rats].

The effect of methyl supplements to the diet of pregnant homozygous (AAHH) female rats with agouti coat color mated with homozygous (aahh) males on the phenotypic modification of the coat color of their heterozygous offspring (AaHh) has been studied. Comparative morphological analysis of the main parameters of hair that determine coat color, including the total length of hairs of different types and the length of the upper black (eumelanin) and light (pheomelanin) parts of awn hairs has been performed. The pattern of pigment granule distribution among hair layers has been analyzed. The melanin content of the hair has been determined using electron spin resonance (ESR). Although all offspring have a typical agouti coat color (alternating black and light portions of hair), 39% of them have a darker coat color than control and other experimental rats have. The main differences between the offspring with darkened and standard coat colors are accounted for by the ratio between the eumelanin and pheomelanin portions of awn hairs. In darkened offspring, this ratio is significantly higher than in control rats. The possible mechanisms of the phenotypic modification of agouti coat color in experimental animals are discussed.

The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

The influence of social disturbance in early life on behavior, response of blood corticosterone level to restraint stress, and endocrine and morphometric indices of the testes was studied in 2-month Norway rat males from three populations: not selected for behavior (unselected), selected for against aggression to humans (tame), and selected for increased aggression to humans (aggressive). The experimental social disturbance included early weaning, daily replacement of cagemates from days 19 to 25, and subsequent housing in twos till the age of 2months. The social disturbance increased the latent period of aggressive behavior in the social interaction test in unselected males and reduced relative testis weights in comparison to the corresponding control groups. In addition, experimental unselected rats had smaller diameters of seminiferous tubules and lower blood testosterone levels. In the experimental group, tame rats had lower basal corticosterone levels, and aggressive animals had lower hormone levels after restraint stress in comparison to the control. The results suggest that the selection in two directions for attitude to humans modifies the response of male rats to social disturbance in early life. In this regard, the selected rat populations may be viewed as a model for investigation of (1) neuroendocrinal mechanisms responsible for the manifestation of aggression and (2) interaction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems in stress.

Effect of selection for behavior on pituitary-adrenal axis and proopiomelanocortin gene expression in silver foxes (Vulpes vulpes).

Silver foxes from a commercial population (farm bred or unselected for behavior control) and from populations selected for tame behavior and enhanced aggressiveness towards man have been investigated. Plasma cortisol and adrenocorticotropic hormone (ACTH) levels, pituitary ACTH levels, POMC gene expression in the anterior pituitary, and corticotropin-releasing factor (CRF) gene expression in the hypothalamus were assessed. The results indicate that the males from the tame-behavior group have lower plasma cortisol and ACTH levels and POMC gene expression in the anterior pituitary in response to capture and handling in comparison with unselected ones. Foxes from the aggressive behavior group also have lower POMC expression, although plasma cortisol and ACTH levels remain the same as in unselected ones. The three groups of animals show no significant changes in the ACTH level in the pituitary and CRF expression in the hypothalamus.

[The potential fertility, embryonic development and hormonal status of rats selected for their estrous cycle reaction to constant illumination]. / Potentsial'naia plodovitost', émbrional'noe razvitie i gormonal'nyi status krys, selektsionirovannykh po reaktsii éstral'nogo tsikla na postoiannoe osveshchenie.

Illumination responsiveness (IR) is studied by selection experiments with outbred Wistar rats. Under selection is estrous cycles under permanent illumination (PI) condition, changes in hormonal status, potential fertility, and embryonic developments ats different stages are registered and compared with control. Results indicate significant changes in endocrine regulatory system in the lines exposed to PI. Functional potentiality of reproductive system gets more weak as a result of this selection, which leads to decreasing in number of ovulations, defective development of placenta, less embryo weights, higher embryo mortality. The opposite conditions are observed in rats undergone selection of stability of estrous cycle. It is concluded that the above selection reveals formation of regulatory mechanisms of reproduction on different genetical physiological bases.

[Gonadal and adrenal endocrine functions in female minks of 2 genotypes in postnatal ontogeny]. / Endokrinnaia funktsiia gonad i nadpochechnikov u samok norok dvukh genotipov v postnatal'nom ontogeneze.

Radioimmune assay has been made of the content of estradiol and progesterone in the blood (from July to March including the 7th day after mating), as well as on the level of estradiol and progesterone production in young females of the standard and mutant sapphire minks in November. It was shown that within certain periods, estradiol and progesterone content of the blood was significantly higher in the standard animals. Gonadal production of estradiol, as well as progesterone production both by the gonads and adrenals in November, were similar in females of both genotypes. It is suggested that sapphire minks have another pattern of correlation between estradiol content of the blood and gonadal production of estradiol as compared to that in standard animals.

[Adrenal function in the mink Mustela vison selected for the type of behavior]. / Funktsiia nadpochechnikov u norok Mustela vison, selektsioniruemykh po tipu povedeniia.

Glucocorticoid function of adrenals and its reactivity to stress caused by immobilization and to ACTH stimulation have been studied in the male minks selected both for domestic and aggressive behavior towards man. In autumn period the regression of cortisol content in adrenals was observed in domesticated males and particularly in aggressive ones compared with control. At the same period the increased level of cortisol in blood as the result of immobilization was noticed in aggressive minks compared with the domesticated and control ones. At ACTH stimulation in spring time the increase of cortisol level in blood was shown for animals of all the groups but it was more marked for the aggressive ones.

Relationship between behavioral selection and primary and secondary immune response in wild gray rats.

The main characteristics of primary and secondary immune response (number of antibody producing cells and the amount of produced antibodies) are reduced in rats selected by elimination of aggressive behavior in comparison with animals selected by stimulation of this behavior. In parallel, the reaction of the pituitary-adrenal system during immune response was modified in these rats. Presumably, the differences in immune reactions of rats selected by contrast behavior are determined by changes in reactivity of the pituitary-adrenal system to stress and immune stimulation during selection.

Gonadal function in mink under artificial photoperiods.

Exposure of juvenile minks to artificial light conditions imitating early autumn (additional illumination from 20 June to 20 July followed by 8 h daylight from 21 July to 10 October--photoperiod I; 8 h daylight from 21 July to 10 October--photoperiod II) induced the prolonged modification of sex steroid concentrations. The increase in plasma testosterone concentrations during the prepubertal period was followed by a decrease before and during the mating period in experimental males. The concentration of oestradiol in plasma increased just before the start of the mating period (January and February) in females under photoperiod I, and these hormonal changes were accompanied by an increase in fertility. The conditions of photoperiod II (involving fewer hours of daylight) had less effect on the sex steroid concentration in the blood of females, and fertility was not changed. The response of gonads to hCG injection at the beginning of puberty (November) was higher in males exposed to photoperiod I conditions and in females exposed to both photoperiods than in control animals.

[Effect of repeated stress on the function of pituitary-adrenal and immune systems in gray rats selected for behavior]. / Vliianie povtoriaiushchegosia stressa na funktsiiu gipofizarno-nadpochechnikovoi i immunnoi sistem u serykh krys, selektsioniruemykh po povedeniiu.

Reaction of pituitary-adrenal axis to a 10-day immobilisation stress and a humoral immune response to subsequent injection of sheep red blood cells were investigated in gray rats selected for enhancement of decrease of aggressive behavior towards humans. It was show that pituitary-adrenal axis reaction of aggressive animals to repeated stress did not change during the experiment, while a decrease of stress-induced corticosterone level was observed already on day 5 of stress. Repeated stress led to enhancement of humoral immune response in aggressive rats, whereas it did not bring about any change in tame animals. based on the obtained data, it could be supposed that breeding of gray rats for domesticated behavior led a faster adaptation to repeated stress and the absence of stimulating influence on humoral immune response in tame rats.