Molecular characterization of the mouse agouti locus

Bultman, Scott J.; Michaud, Edward J.; Woychik, Richard P.

doi:10.1016/s0092-8674(05)80067-4

Cited by 754 publications

(530 citation statements)

References 42 publications

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“…This phenomenon is explained by alternative promoter use in the agouti gene [4,15,20,23]. In this respect, the blue fox mutation act as a classical constitutively activated MC1R mutation in being epistatic to the agouti gene.…”

Section: Resultsmentioning

confidence: 99%

Two cysteine substitutions in the MC1R generate the blue variant of the arctic fox (Alopex lagopus) and prevent expression of the white winter coat

et al. 2005

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We have characterized two mutations in the MC1R gene of the blue variant of the arctic fox (Alopex lagopus) that both incorporate a novel cysteine residue into the receptor. A family study in farmed arctic foxes verified that the dominant expression of the blue color phenotype cosegregates completely with the allele harboring these two mutations. Additionally to the altered pigment synthesis, the blue fox allele suppresses the seasonal change in coat color found in the native arctic fox. Consequently, these findings suggest that the MC1R/agouti regulatory system is involved in the seasonal changes of coat color found in arctic fox.

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Section: Resultsmentioning

confidence: 99%

Two cysteine substitutions in the MC1R generate the blue variant of the arctic fox (Alopex lagopus) and prevent expression of the white winter coat

et al. 2005

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“…Two main loci (Agouti and Extension) control and regulate the relative amount of these two melanin types in skin and hair (Searle, 1968). The Agouti locus encodes for the agouti signalling protein (ASIP; Bultman et al, 1992). This small paracrine signalling molecule interacts with the -E-mail: luca.fontanesi@unibo.it product of the Extension locus that encodes for the melanocortin 1 receptor (MC1R).…”

Section: Introductionmentioning

confidence: 99%

“…A large number of alleles have been described at the Agouti locus in mice, with most having been characterized at the DNA level (e.g. Bultman et al, 1992;Miltenberger et al, 2002). Mutations at this locus affecting or associated with coat colours or skin pigmentation have been also identified in other species.…”

Section: Introductionmentioning

confidence: 99%

Coat colours in the Massese sheep breed are associated with mutations in the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes

Fontanesi

Dall’Olio

Beretti

et al. 2011

Animal

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Massese is an Italian dairy sheep breed characterized by animals with black skin and horns and black or apparent grey hairs. Owing to the presence of these two coat colour types, this breed can be considered an interesting model to evaluate the effects of coat colour gene polymorphisms on this phenotypic trait. Two main loci have been already shown to affect coat colour in sheep: Agouti and Extension coding for the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes, respectively. The Agouti locus is affected by a large duplication including the ASIP gene that may determine the Agouti white and tan allele (A Wt ). Other disrupting or partially inactivating mutations have been identified in exon 2 (a deletion of 5 bp, D 5 ; and a deletion of 9 bp, D 9 ) and in exon 4 (g.5172T.A, p.C126S) of the ASIP gene. Three missense mutations in the sheep MC1R gene cause the dominant black E D allele (p.M73K and p.D121N) and the putative recessive e allele (p.R67C). Here, we analysed these ASIP and MC1R mutations in 161 Massese sheep collected from four flocks. The presence of one duplicated copy allele including the ASIP gene was associated with grey coat colour (P 5 9.4E-30). Almost all animals with a duplicated copy allele (37 out of 41) showed uniform apparent grey hair and almost all animals without a duplicated allele (117 out of 120) were completely black. Different forms of duplicated alleles were identified in Massese sheep including, in almost all cases, copies with exon 2 disrupting or partially inactivating mutations making these alleles different from the A Wt allele. A few exceptions were observed in the association between ASIP polymorphisms and coat colour: three grey sheep did not carry any duplicated copy allele and four black animals carried a duplicated copy allele. Of the latter four sheep, two carried the E D allele of the MC1R gene that may be the cause of their black coat colour. The coat colour of all other black animals may be determined by non-functional ASIP alleles (non-agouti alleles, A a ) and in a few cases by the E D Extension allele. At least three frequent ASIP haplotypes ([D 5 :g.5172T], [N:g.5172A] and [D 5 :g.5172A]) were detected (organized into six different diplotypes). In conclusion, the results indicated that coat colours in the Massese sheep breed are mainly derived by combining ASIP and MC1R mutations.

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“…The MC4R gene is localized on chromosome 18q21.32 and encodes a complex plasma membrane protein that belongs to the seven transmembrane G protein-coupled receptor family that activates adenylate cyclase to produce cyclic adenosine monophosphate (cAMP) during signal transduction (Magenis et al 1994;Yang et al 2000). The first evidence indicating that the MC4R gene was associated with regulating energy balance resulted from mice possessing a targeted disruption of the Mc4r gene (Bultman et al 1992;Huszar et al 1997). These studies demonstrated that Mc4r heterozygous (Mc4r ?/-) mice were susceptible to intermediate weight gain compared to Mc4r normal (Mc4r ?/? )…”

Section: Obesity Susceptibility Genes That Interact With Dietary Fatsmentioning

confidence: 99%

The genetics of childhood obesity and interaction with dietary macronutrients

et al. 2013

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The genes contributing to childhood obesity are categorized into three different types based on distinct genetic and phenotypic characteristics. These types of childhood obesity are represented by rare monogenic forms of syndromic or non-syndromic childhood obesity, and common polygenic childhood obesity. In some cases, genetic susceptibility to these forms of childhood obesity may result from different variations of the same gene. Although the prevalence for rare monogenic forms of childhood obesity has not increased in recent times, the prevalence of common childhood obesity has increased in the United States and developing countries throughout the world during the past few decades. A number of recent genome-wide association studies and mouse model studies have established the identification of susceptibility genes contributing to common childhood obesity. Accumulating evidence suggests that this type of childhood obesity represents a complex metabolic disease resulting from an interaction with environmental factors, including dietary macronutrients. The objective of this article is to provide a review on the origins, mechanisms, and health consequences of obesity susceptibility genes and interaction with dietary macronutrients that predispose to childhood obesity. It is proposed that increased knowledge of these obesity susceptibility genes and interaction with dietary macronutrients will provide valuable insight for individual, family, and community preventative lifestyle intervention, and eventually targeted nutritional and medicinal therapies.

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Molecular characterization of the mouse agouti locus

Cited by 754 publications

References 42 publications

Two cysteine substitutions in the MC1R generate the blue variant of the arctic fox (Alopex lagopus) and prevent expression of the white winter coat

Two cysteine substitutions in the MC1R generate the blue variant of the arctic fox (Alopex lagopus) and prevent expression of the white winter coat

Coat colours in the Massese sheep breed are associated with mutations in the agouti signalling protein (ASIP) and melanocortin 1 receptor (MC1R) genes

The genetics of childhood obesity and interaction with dietary macronutrients

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