A molecular analysis of the patterns of genetic diversity in local chickens from western Algeria in comparison with commercial lines and wild jungle fowls.

The objectives of this study were to characterize the genetic variability of village chickens from three agro-ecological regions of western Algeria: coastal (CT), inland plains (IP) and highlands (HL), to reveal any underlying population structure, and to evaluate potential genetic introgression from commercial lines into local populations. A set of 233 chickens was genotyped with a panel of 23 microsatellite markers. Geographical coordinates were individually recorded. Eight reference populations were included in the study to investigate potential gene flow: four highly selected commercial pure lines and four lines of French slow-growing chickens. Two populations of wild red jungle fowls were also genotyped to compare the range of diversity between domestic and wild fowls. A genetic diversity analysis was conducted both within and between populations. Multivariate redundancy analyses were performed to assess the relative influence of geographical location among Algerian ecotypes. The results showed a high genetic variability within the Algerian population, with 184 alleles and a mean number of 8.09 alleles per locus. The values of heterozygosity (He and Ho) ranged from 0.55 to 0.62 in Algerian ecotypes and were smaller than values found in Jungle fowl populations and higher than values found in commercial populations. Although the structuring analysis of genotypes did not reveal clear subpopulations within Algerian ecotypes, the supervised approach using geographical data showed a significant (p < 0.01) differentiation between the three ecotypes which was mainly due to altitude. Thus, the genetic diversity of Algerian ecotypes may be under the influence of two factors with contradictory effects: the geographical location and climatic conditions may induce some differentiation, whereas the high level of exchanges and gene flow may suppress it. Evidence of gene flow between commercial and Algerian local populations was observed, which may be due to unrecorded crossing with commercial chickens. Chicken ecotypes from western Algeria are characterized by a high genetic diversity and must be safeguarded as an important reservoir of genetic diversity.

Robustness to chronic heat stress in laying hens: a meta-analysis.

Chronic heat is a major stress factor in laying hens and many studies on the effect of heat stress have been published. It remains difficult, however, to draw general conclusions about the effect of chronic heat stress on performance and its relationship with genetic and environmental factors, as these studies have been done under varying experimental conditions and using various experimental designs. A meta-analysis enabled us to make a quantitative review of the results from 131 published papers. The relative effects of four factors (genotype, age, group size, and amplitude of temperature variation) and their interactions with temperature were analyzed for 13 traits. After pre-correcting the data for a random study effect, the best model for each trait was selected in a stepwise procedure based on its residual sum of squares. Shell strength, daily feed intake, egg mass, and hen-day egg production were found to be more sensitive to heat stress than the other traits as they dropped by 9.0 to 22.6% between thermo-neutrality (15 to 20°C) and heat stress (30 to 35°C) while yolk and albumen proportions or Haugh units showed nearly no variation with temperature (<1.2% between thermo-neutrality and heat stress). Many interactions (17) were found between temperature and one or more factors in the 13 traits studied here, which reinforces the interest of using a meta-analysis to summarize data from the literature. This study highlighted that the impact of heat stress in laying hens depends on the genotype, age, and group size, some of which have rarely been investigated.

Genetic diversity of Vietnamese domestic chicken populations as decision-making support for conservation strategies.

The aims of this study were to assess the genetic diversity of 17 populations of Vietnamese local chickens (VNN) and one Red Jungle Fowl population, together with six chicken populations of Chinese origin (CNO), and to provide priorities supporting the conservation of genetic resources using 20 microsatellites. Consequently, the VNN populations exhibited a higher diversity than did CNO populations in terms of number of alleles but showed a slightly lower observed heterozygosity. The VNN populations showed in total seven private alleles, whereas no CNO private alleles were found. The expected heterozygosity of 0.576 in the VNN populations was higher than the observed heterozygosity of 0.490, leading to heterozygote deficiency within populations. This issue could be partly explained by the Wahlund effect due to fragmentation of several populations between chicken flocks. Molecular analysis of variance showed that most of genetic variation was found within VNN populations. The Bayesian clustering analysis showed that VNN and CNO chickens were separated into two distinct groups with little evidence for gene flow between them. Among the 24 populations, 13 were successfully assigned to their own cluster, whereas the structuring was not clear for the remaining 11 chicken populations. The contributions of 24 populations to the total genetic diversity were mostly consistent across two approaches, taking into account the within- and between-populations genetic diversity and allelic richness. The black H'mong, Lien Minh, Luong Phuong and Red Jungle Fowl were ranked with the highest priorities for conservation according to Caballero and Toro's and Petit's approaches. In conclusion, a national strategy needs to be set up for Vietnamese chicken populations, with three main components: conservation of high-priority breeds, within-breed management with animal exchanges between flocks to avoid Wahlund effect and monitoring of inbreeding rate.

A global analysis of molecular markers and phenotypic traits in local chicken breeds in Taiwan.

Molecular and phenotypic data have been combined to characterize the genetic diversity of six local chicken breeds maintained with a long-term conservation programme. Hua-Tung, Hsin-Yi, Ju-Chi and Quemoy originated from Taiwan, Shek-Ki is from South China, and Nagoya is from Japan. Molecular tools included 24 microsatellite markers, melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) (MC1R), the LEI0258 marker located within the major histocompatibility complex (MHC), and mitochondrial DNA. Performance was recorded on the same individuals for body weight, panting rate in summer and antibody response (antigens: Newcastle disease virus and sheep red blood cells). A multivariate method previously proposed for taxonomy was used to combine the different data sets. Melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) and the MCW330 marker contributed the most to the first axis of the multiple coinertia analysis of molecular markers. Melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) showed evidence of selection, probably related to its effect on feather colour. The MHC exhibited a large diversity, with 16 alleles of the LEI0258 marker. Immune response traits contributed the most to the principal component analysis of phenotypic data. Eight mitochondrial DNA haplotypes related to clades A, B, C and E were distributed across breeds and revealed an important contribution of Indian and European breeds to Ju-Chi, Quemoy and Hsin-Yi. Phenotypic data contributed less than molecular data to the combined analysis, and two markers, LEI0258 and LEI0228, contributed the most. The combined analysis could clearly discriminate all breeds, except Ju-Chi, which was similar to Quemoy for many criteria, except immune response.

Vietnamese chickens: a gate towards Asian genetic diversity.

BACKGROUND: Chickens represent an important animal genetic resource and the conservation of local breeds is an issue for the preservation of this resource. The genetic diversity of a breed is mainly evaluated through its nuclear diversity. However, nuclear genetic diversity does not provide the same information as mitochondrial genetic diversity. For the species Gallus gallus, at least 8 maternal lineages have been identified. While breeds distributed westward from the Indian subcontinent usually share haplotypes from 1 to 2 haplogroups, Southeast Asian breeds exhibit all the haplogroups. The Vietnamese Ha Giang (HG) chicken has been shown to exhibit a very high nuclear diversity but also important rates of admixture with wild relatives. Its geographical position, within one of the chicken domestication centres ranging from Thailand to the Chinese Yunnan province, increases the probability of observing a very high genetic diversity for maternal lineages, and in a way, improving our understanding of the chicken domestication process. RESULTS: A total of 106 sequences from Vietnamese HG chickens were first compared to the sequences of published Chinese breeds. The 25 haplotypes observed in the Vietnamese HG population belonged to six previously published haplogroups which are: A, B, C, D, F and G. On average, breeds from the Chinese Yunnan province carried haplotypes from 4.3 haplogroups. For the HG population, haplogroup diversity is found at both the province and the village level (0.69).The AMOVA results show that genetic diversity occurred within the breeds rather than between breeds or provinces. Regarding the global structure of the mtDNA diversity per population, a characteristic of the HG population was the occurrence of similar pattern distribution as compared to G. gallus spadiceus. However, there was no geographical evidence of gene flow between wild and domestic populations as observed when microsatellites were used. CONCLUSIONS: In contrast to other chicken populations, the HG chicken population showed very high genetic diversity at both the nuclear and mitochondrial levels. Due to its past and recent history, this population accumulates a specific and rich gene pool highlighting its interest and the need for conservation.

Integrating geo-referenced multiscale and multidisciplinary data for the management of biodiversity in livestock genetic resources.

In livestock genetic resource conservation, decision making about conservation priorities is based on the simultaneous analysis of several different criteria that may contribute to long-term sustainable breeding conditions, such as genetic and demographic characteristics, environmental conditions, and role of the breed in the local or regional economy. Here we address methods to integrate different data sets and highlight problems related to interdisciplinary comparisons. Data integration is based on the use of geographic coordinates and Geographic Information Systems (GIS). In addition to technical problems related to projection systems, GIS have to face the challenging issue of the non homogeneous scale of their data sets. We give examples of the successful use of GIS for data integration and examine the risk of obtaining biased results when integrating datasets that have been captured at different scales.

Objectives, criteria and methods for using molecular genetic data in priority setting for conservation of animal genetic resources.

The genetic diversity of the world's livestock populations is decreasing, both within and across breeds. A wide variety of factors has contributed to the loss, replacement or genetic dilution of many local breeds. Genetic variability within the more common commercial breeds has been greatly decreased by selectively intense breeding programmes. Conservation of livestock genetic variability is thus important, especially when considering possible future changes in production environments. The world has more than 7500 livestock breeds and conservation of all of them is not feasible. Therefore, prioritization is needed. The objective of this article is to review the state of the art in approaches for prioritization of breeds for conservation, particularly those approaches that consider molecular genetic information, and to identify any shortcomings that may restrict their application. The Weitzman method was among the first and most well-known approaches for utilization of molecular genetic information in conservation prioritization. This approach balances diversity and extinction probability to yield an objective measure of conservation potential. However, this approach was designed for decision making across species and measures diversity as distinctiveness. For livestock, prioritization will most commonly be performed among breeds within species, so alternatives that measure diversity as co-ancestry (i.e. also within-breed variability) have been proposed. Although these methods are technically sound, their application has generally been limited to research studies; most existing conservation programmes have effectively primarily based decisions on extinction risk. The development of user-friendly software incorporating these approaches may increase their rate of utilization.

Genetic analysis of local Vietnamese chickens provides evidence of gene flow from wild to domestic populations.

UNLABELLED: Previous studies suggested that multiple domestication events in South and South-East Asia (Yunnan and surrounding areas) and India have led to the genesis of modern domestic chickens. Ha Giang province is a northern Vietnamese region, where local chickens, such as the H'mong breed, and wild junglefowl coexist. The assumption was made that hybridisation between wild junglefowl and Ha Giang chickens may have occurred and led to the high genetic diversity previously observed. The objectives of this study were i) to clarify the genetic structure of the chicken population within the Ha Giang province and ii) to give evidence of admixture with G. gallus. A large survey of the molecular polymorphism for 18 microsatellite markers was conducted on 1082 chickens from 30 communes of the Ha Giang province (HG chickens). This dataset was combined with a previous dataset of Asian breeds, commercial lines and samples of Red junglefowl from Thailand and Vietnam (Ha Noï). Measurements of genetic diversity were estimated both within-population and between populations, and a step-by-step Bayesian approach was performed on the global data set. RESULTS: The highest value for expected heterozygosity (> 0.60) was found in HG chickens and in the wild junglefowl populations from Thailand. HG chickens exhibited the highest allelic richness (mean A = 2.9). No significant genetic subdivisions of the chicken population within the Ha Giang province were found. As compared to other breeds, HG chickens clustered with wild populations. Furthermore, the neighbornet tree and the Bayesian clustering analysis showed that chickens from 4 communes were closely related to the wild ones and showed an admixture pattern. CONCLUSION: In the absence of any population structuring within the province, the H'mong chicken, identified from its black phenotype, shared a common gene pool with other chickens from the Ha Giang population. The large number of alleles shared exclusively between Ha Giang chickens and junglefowl, as well as the results of a Bayesian clustering analysis, suggest that gene flow has been taking place from junglefowl to Ha Giang chickens.

Using molecular markers and multivariate methods to study the genetic diversity of local European and Asian chicken breeds.

French and Asian subsets of chicken breeds were first analysed using 22 microsatellites and then compared to the AVIANDIV European set using 14 loci. Positive correlations were observed between F(IT) or F(ST) and typological values or variance of markers using the multivariate analysis mcoa. The first axis of the multivariate representation separated Asian from European breeds, revealing breeds with Asian ancestor. Using all or 14 loci, correct assignation rate was always higher than 93%. The Weitzman index and the aggregate diversity D were calculated using 22 loci within French and Asian breeds. The French breed Coucou de Rennes and the Hua-Tung breed seemed to contribute the most to the global diversity of each subset. This approach on French-only breeds and then on French with AVIANDIV domestic breeds (14 loci) showed that the Marans breed contributed the most. The AVIANDIV framework could be useful to evaluate the genetic diversity of local breeds and to help in connecting national and regional conservation policies.

Molecular genotype investigation of the Gallus gallus major histocompatibility complex.

The association between genetic markers and serological major histocompatibility complex (MHC) definition was studied in experimental White Leghorn lines selected for different immune traits. Different markers, three variable number tandem repeats (VNTRs) and 10 single nucleotide polymorphisms (SNPs), distributed along the MHC sequence were genotyped. Correlation between VNTR marker alleles and serology was studied in more than 800 animals and correspondence between SNP haplotypes and allele size was defined. A complete table of correspondence between VNTR allele sizes, SNP genotypes and serology was then drawn. This research shows that integrating new molecular tools can definitely help in MHC haplotype characterization and that, since the chicken MHC locus has been associated with disease resistance, these tools are becoming more and more needed for disease resistance and immunogenomics studies.

Effect of introducing the naked neck gene in a line selected for low residual feed consumption on performance in temperate or subtropical environments.

The aim of this study was to investigate the possibility of combining the naked neck gene with a genetic background that has been optimized for feed efficiency of laying hens at moderate temperature. In 1997, the naked neck gene was introduced into a line selected for low residual feed intake. In 2003, after 6 generations of introgression, 8 males and 56 females heterozygous for the NA*NA mutation were used to generate all 3 genotypes (NA*N/NA*N, NA*NA/NA*N, NA*NA/NA*NA), in 2 hatches, for rearing in Taiwan and France, respectively, at 3-wk intervals. Growth performance, anatomical traits, laying traits, and feed efficiency were recorded in each country. In addition, comb and rectal temperatures were measured in Taiwan. Performance was generally lower and mortality of laying hens was higher in Taiwan (11%) than in France (1%). Genotype x environment interactions were rare: genotype x environment was observed only for body weight at 10 wk of age and was close to significance for egg weight. The laying performance was significantly decreased in Taiwan by about 25%. The naked neck genotype had a negative effect on body weight and a positive effect of clutch length and egg weight. It also affected heat dissipation traits such as wattle length and rectal and surface temperature measurements. There was a clear additive and negative effect of the NA*NA mutation on rectal temperature. Feed intake and residual feed intake were increased in the homozygous carriers of the NA*NA mutation, which may improve heat tolerance of the low residual feed consumption (R-) line. Feed efficiency tended to be better in NA*NA/NA*NA hens in both environments. Thus, the introduction of the NA*NA mutation in the R- background appeared to be favorable from the viewpoint of feed efficiency, but it did not improve laying performance in a subtropical environment. Other factors than temperature, such as diet composition and lighting regimen, may be involved.

A high-resolution linkage map for the Z chromosome in chicken reveals hot spots for recombination.

A comprehensive linkage map for chicken chromosome Z was constructed as the result of a large-scale screening of single nucleotide polymorphisms (SNPs). A total of 308 SNPs were assigned to Z based on the genotype distribution among 182 birds representing several populations. A linkage map comprising 210 markers and spanning 200.9 cM was established by analyzing a small Red junglefowl/White Leghorn intercross. There was excellent agreement between the linkage map for Z and a recently released assembly of the chicken genome (May 2006). Almost all SNPs assigned to chromosome Z in the present study are on Z in the new genome assembly. The remaining 12 loci are all found on unassigned contigs that can now be assigned to Z. The average recombination rate was estimated at 2.7 cM/Mb but there was a very uneven distribution of recombination events with both cold and hot spots of recombination. The existence of one of the major hot spots of recombination, located around position 39.4 Mb, was supported by the observed pattern of linkage disequilibrium. Thirteen markers from unassigned contigs were shown to be located on chromosome W. Three of these contigs included genes that have homologues on chromosome Z. The preliminary assignment of three more genes to the gene-poor W chromosome may be important for studies on the mechanism of sex determination and dosage compensation in birds.

Semen cryopreservation for ex situ management of genetic diversity in chicken: creation of the French avian cryobank.

The need for semen preservation in domestic birds is a result of the reduction in genetic variability of domestic bird livestock and of the increasing risk of line extinction for health and safety reasons. Cryopreservation of embryos and primordial germ cells (PGC) is not routinely feasible in birds. The project therefore involved semen frozen in optimal safety and traceable conditions. Whole blood samples were also frozen to provide samples of analyses of genomes and health status. The feasibility of using ex situ conservation, i.e., collecting biological material to be stored outside the usual production area of the species (ex situ genetic stock), to preserve and manage rare breeds was tested with 4 subfertile populations: 3 rare experimental lines used for research into energy metabolism (R+), growth (Y33), and immunity (B4/B4), reared under known health status and the oldest endangered patrimonial French breed, the Gauloise dorée with an unknown health status. A general infrastructure was set up for the health screening and remediation of diseases, collection and storage of frozen cells and 2 sites were created for the storage of frozen samples. The screening and remediation of diseases of the Gauloise dorée, which was contaminated with various Salmonella and Mycoplasma strains, was achieved by successive treatment of parents, incubated eggs and young chicks with Baytril followed by Tiamulin. For each line, 474 to 994 semen straws have been frozen, thawed, and the semen evaluated. Insemination of frozen-thawed semen into females of the same genetic origin or of an egg-type commercial breed produced chicks in every case. For the most subfertile lines, insemination with egg-type females significantly increased the reproductive success. In conclusion, we report on the benefits of a semen and blood cryobanking complex for the management of endangered lines and strains of domestic birds. Current stocks made possible the restoration of more than 96% of the initial genome. This project also provided technical solutions to resolve some of the health problems frequently encountered for gene preservation in poultry.

Heritability of body surface temperature in hens estimated by infrared thermography at normal or hot temperatures and genetic correlations with egg and feather quality.

Exposure of laying hens to chronic heat stress results in loss of egg production. It should be possible to improve hen resilience to chronic heat stress by genetic selection but measuring their sensitivity through internal temperature is time consuming and is not very precise. In this study we used infrared thermography to measure the hen's capacity to dissipate heat, in a commercial line of laying hens subjected to cycles of neutral (N, 19.6°C) or high (H, 28.4°C) ambient temperatures. Mean body temperatures (BT) were estimated from 9355 infrared images of wing, comb and shank taken from 1200 hens. Genetic parameters were estimated separately for N and H temperatures. Correlations between BT and plumage condition were also investigated. Wing temperature had low heritability (0.00 to 0.09), consistent with the fact that wing temperature mainly reflects the environmental temperature and is not a zone of heat dissipation. The heritability of comb temperature was higher, from 0.15 to 0.19 in N and H conditions, respectively. Finally, the shank temperature provided the highest heritability estimates, with values of 0.20 to 0.22 in H and N conditions, respectively. Taken together, these results show that heat dissipation is partly under genetic control. Interestingly, the genetic correlation between plumage condition and shank and comb temperatures indicated that birds with poor condition plumage also had the possibility to dissipate heat through featherless areas. Genetic correlations of temperature measurements with egg quality showed that temperatures were correlated with egg width and weight, yolk brightness and yellowness and Haugh units only under H conditions. In contrast, shell colour was correlated with leg temperature only at thermo-neutrality.

Review: Towards the agroecological management of ruminants, pigs and poultry through the development of sustainable breeding programmes. II. Breeding strategies.

Agroecology uses ecological processes and local resources rather than chemical inputs to develop productive and resilient livestock and crop production systems. In this context, breeding innovations are necessary to obtain animals that are both productive and adapted to a broad range of local contexts and diversity of systems. Breeding strategies to promote agroecological systems are similar for different animal species. However, current practices differ regarding the breeding of ruminants, pigs and poultry. Ruminant breeding is still an open system where farmers continue to choose their own breeds and strategies. Conversely, pig and poultry breeding is more or less the exclusive domain of international breeding companies which supply farmers with hybrid animals. Innovations in breeding strategies must therefore be adapted to the different species. In developed countries, reorienting current breeding programmes seems to be more effective than developing programmes dedicated to agroecological systems that will struggle to be really effective because of the small size of the populations currently concerned by such systems. Particular attention needs to be paid to determining the respective usefulness of cross-breeding v. straight breeding strategies of well-adapted local breeds. While cross-breeding may offer some immediate benefits in terms of improving certain traits that enable the animals to adapt well to local environmental conditions, it may be difficult to sustain these benefits in the longer term and could also induce an important loss of genetic diversity if the initial pure-bred populations are no longer produced. As well as supporting the value of within-breed diversity, we must preserve between-breed diversity in order to maintain numerous options for adaptation to a variety of production environments and contexts. This may involve specific public policies to maintain and characterize local breeds (in terms of both phenotypes and genotypes), which could be used more effectively if they benefited from the scientific and technical resources currently available for more common breeds. Last but not least, public policies need to enable improved information concerning the genetic resources and breeding tools available for the agroecological management of livestock production systems, and facilitate its assimilation by farmers and farm technicians.

Review: Towards the agroecological management of ruminants, pigs and poultry through the development of sustainable breeding programmes: I-selection goals and criteria.

Agroecology uses natural processes and local resources rather than chemical inputs to ensure production while limiting the environmental footprint of livestock and crop production systems. Selecting to achieve a maximization of target production criteria has long proved detrimental to fitness traits. However, since the 1990s, developments in animal breeding have also focussed on animal robustness by balancing production and functional traits within overall breeding goals. We discuss here how an agroecological perspective should further shift breeding goals towards functional traits rather than production traits. Breeding for robustness aims to promote individual adaptive capacities by considering diverse selection criteria which include reproduction, animal health and welfare, and adaptation to rough feed resources, a warm climate or fluctuating environmental conditions. It requires the consideration of genotype×environment interactions in the prediction of breeding values. Animal performance must be evaluated in low-input systems in order to select those animals that are adapted to limiting conditions, including feed and water availability, climate variations and diseases. Finally, we argue that there is no single agroecological animal type, but animals with a variety of profiles that can meet the expectations of agroecology. The standardization of both animals and breeding conditions indeed appears contradictory to the agroecological paradigm that calls for an adaptation of animals to local opportunities and constraints in weakly artificialized systems tied to their physical environment.

Empirical evaluation of genetic clustering methods using multilocus genotypes from 20 chicken breeds.

We tested the utility of genetic cluster analysis in ascertaining population structure of a large data set for which population structure was previously known. Each of 600 individuals representing 20 distinct chicken breeds was genotyped for 27 microsatellite loci, and individual multilocus genotypes were used to infer genetic clusters. Individuals from each breed were inferred to belong mostly to the same cluster. The clustering success rate, measuring the fraction of individuals that were properly inferred to belong to their correct breeds, was consistently approximately 98%. When markers of highest expected heterozygosity were used, genotypes that included at least 8-10 highly variable markers from among the 27 markers genotyped also achieved >95% clustering success. When 12-15 highly variable markers and only 15-20 of the 30 individuals per breed were used, clustering success was at least 90%. We suggest that in species for which population structure is of interest, databases of multilocus genotypes at highly variable markers should be compiled. These genotypes could then be used as training samples for genetic cluster analysis and to facilitate assignments of individuals of unknown origin to populations. The clustering algorithm has potential applications in defining the within-species genetic units that are useful in problems of conservation.

A naturally occurring growth hormone receptor mutation: in vivo and in vitro evidence for the functional importance of the WS motif common to all members of the cytokine receptor superfamily.

To obtain an animal model for studying the role of the GH receptor (GHR) in growth and development, we analyzed a sex-linked dwarf (SLD) chicken strain (Leghorn) which exhibits phenotype similarities with a human genetic growth disorder, an autosomal recessive GH resistance condition (Laron dwarfism). Having previously demonstrated the responsibility of the human GHR gene in the Laron phenotype, we focused our analysis on the corresponding gene in SLD chickens. Sequencing of the whole coding region of the chicken GHR cDNA identified a G-to-T transversion segregating with the SLD phenotype and generating an isoleucine instead of a serine at position 199 within a highly conserved region close to the junction between the extracellular and transmembrane domains. This defect involves the last invariant amino acid of the WS-like motif (amino acid sequence WSXWS) common to all members of the cytokine receptor superfamily. Transfection of a mutated GHR cDNA containing this mutation into eukaryotic cells led to the synthesis of a receptor protein that displayed impaired plasma membrane expression and binding activity. These data define the molecular basis for the SLD phenotype and identify this strain as an interesting model for studying Laron dwarfism in humans; this animal model may also represent a system in which therapeutic strategies to promote growth can be evaluated. Finally, the nature of the molecular defect identified provides direct evidence for the functional importance of the WS motif in GHRs and related receptors.

Increased in-vivo insulin sensitivity but normal liver insulin receptor kinase activity in dwarf chickens.

The effects of the recessive and sex-linked dw gene on insulin sensitivity and liver insulin receptors were compared in normal (Dw-dw) and dwarf (dw-dw) brother or half-brother chickens. At 3.5 weeks of age, following an overnight fast, exogenous insulin (0-6.9 nmol/kg body weight) was slightly but significantly more hypoglycaemic in dwarf chickens. At 4 weeks of age, following an oral glucose load (2 g/kg), glucose tolerance was the same in both genotypes, whereas plasma insulin levels were greatly decreased in dwarf chickens. At 5 weeks of age, plasma concentrations of glucose and insulin were the same in both genotypes in the fasting state and decreased in the fed state in dwarf chickens. In liver membranes prepared from fasted chickens, insulin binding was increased in dwarf chickens, while the affinity of insulin receptors and the insulin-degrading activity of the membranes were the same in both genotypes. Following solubilization with Triton X-100, liver receptors were successively purified on lentil then wheat germ lectins. Autophosphorylation of the beta-subunit did not differ between either the genotype or the nutritional (fed or fasted) state. In the basal state (in the absence of insulin) the tyrosine kinase activity of the receptor towards artificial substrate poly(Glu, Tyr)4:1 was significantly decreased in dwarf chickens by fasting. However, the change in tyrosine kinase activity of the receptor in response to insulin was similar, irrespective of the genotype and the nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of insulin-like growth factor-I (IGF-I) infusion and dietary tri-iodothyronine (T3) supplementation on growth, body composition and plasma hormone levels in sex-linked dwarf mutant and normal chickens.

This study used a sex-linked dwarf mutant (SLD) chicken to evaluate growth-promoting and metabolic effects of recombinant human insulin-like growth factor-I (rhIGF-I) treatment. The SLD chicken is characterized by a 30% reduction in body weight and by high plasma GH levels, low plasma IGF-I and triodothyronine (T3) levels and very low GH binding on liver membranes, suggesting reduced functional GH receptors compared with normal chickens. The effects of a continuous s.c. infusion by osmotic mini-pump of 0.1 mg rhIGF-I/kg per day from 4 to 8 weeks of age on body weight, bone growth and body composition were investigated in female SLD and normal chicks. In addition, half of the birds received a dietary supplement of T3 (0.1 parts per million). Plasma levels of IGF-I, GH, T3, thyroxine and insulin were followed during the treatment. In normal chicks, rhIGF-I infusion had no effect on growth and little effect on plasma hormone levels except for a decrease in plasma insulin. In dwarf chicks, rhIGF-I infusion slightly increased body weight but had no effect on longitudinal bone growth. In addition, plasma GH levels were decreased and T3 levels remained lower than in normal chicks. Normal and dwarf chicks showed a decrease in abdominal fat after both IGF-I administration and T3 supplementation, the treatments having additive effects in dwarf chicks only. The combined rhIGF-I and T3 treatment restored a quasi-normal hormonal pattern in dwarf chicks, except for insulin which remained lower than in normal chicks. These results suggest that IGF-I in the chicken has no direct endocrine effect on statural growth.