The Colors of Mice: A Model Genetic Network

“For example, melaninforming enzymes are not functional unless they enter the melanosomes and become activated in the endoplasmic reticulum (Lamoreux et al., 2010).”

“Failure to migrate or proliferate sufficiently results in the unpigmented patches seen in humans (Fleischman et al., 1991), numerous mouse mutants (Lamoreux et al., 2010) and also in the selectively bred piebald patterns of domestic animals, such as horses and cows (Hauswirth et al., 2012;…”

“The latter reflects the impact of HPS on mouse coat color and the ease with which spontaneous coat color mutants can be detected and propagated.(47,48) Such spontaneous mutations have given rise to at least 15 HPS models in the mouse including correlates of all of the human HPS variants and mutants in genes encoding t…”

“…is more pronounced in the background of mutations at the Tyrp1 locus, encoding the melanogenic enzyme TYRP1 (Dunn and Thigpen, 1930; Hellström et al. , 2011; Lamoreux et al. , 2010), perhaps suggesting that PMEL is most effective in detoxifying intermediates that accumulate in the absence of TYRP1.”

“Among the genetic factors, the coat color genes are the most important (Bennett and Lamoreux, 2003; Hirobe and Abe, 1999; Lamoreux et al., 2001, 2010; Silvers, 1979).”

“In mice, study of pigmentary genetics began more than 100 yr ago (Lamoreux et al., 2010).”

“Mutation of several of these genes, including the three melanogenic enzymes and a few ion transporters, causes oculocutaneous albinism (OCA) in patients and animal models (2, 5, 12).”

“(2016) as these mutations can occur in several genes, as opposed to only in the piebald gene (Lamoreux et al. 2010).”

“The enzyme tyrosinase, naturally present in melanin cells, catalyses melanin synthesis, but due to inheritable causes (mutations) it can become absent or less active, with no or incomplete melanin synthesis as a result (Lamoreux et al. 2010).”

“More than 80 genes have been specifically implicated in melanocyte development, although their precise functions and the times at which they exert their functions are in most cases unknown (Lamoreux et al., 2010) (http://www.espcr.org/micemut/#cloned).”

“The study of vertebrate colour patterns has by and large been restricted to inbred laboratory mice strains (Lamoreux et al. 2010).”

“The receptor tyrosine kinase c-kit is critical for melanocyte migration, and mutations in this gene lead to white midline spots in mice and piebaldism in humans (Lamoreux et al., 2010).”

“DOI: 10.1002/0471143030.cb0108s63 Copyright C© 2014 John Wiley & Sons, Inc. Cell Culture 1.8.1 Supplement 63 (reviewed by Lin and Fisher, 2007, and by Lamoreux et al., 2010).”

“Among NCC-derivatives, melanocytes have been extensively studied because their characteristic color and morphology makes them highly amenable to genetic screening [13,14].”

“However, the number of loci affecting this phenotypic trait is larger than previously expected as, at present, more than 300 loci have been shown to affect coat colour in mice (Lamoureux et al. 2010).”

“These coat color mutants have for many years constituted a unique resource for studying molecules involved in pigmentation and such studies have revealed the involvement of hundreds of genes in the development and the homing of pigment cells, called melanocytes [1].”

“Although more than 200 genes have been linked to coat colour changes in laboratory mice (Silvers, 1979; Lamoreux et al., 2010), two genes, the Agouti signalling protein gene (Asip) and the melanocortin-1 receptor gene (Mc1r), are major determinants of red–yellow and black–brown colour variations in vertebrates (Hubbar…”

“These pigmentation loci were originally identified in mice and other animals, and are known to have conserved functions in melanin deposition across mammals, including humans (Lamason et al. 2005; Nordlund et al. 2006; Sponenberg 2009; Lamoreux et al. 2010; see also the Results and Discussion).”

“The development of the mouse fancy, and the subsequent institutionalization of this in the twentieth century, provided a fertile resource for those keen to understand mammalian biology (Lamoreux et al., 2010).”

“Mutations in key genes affecting these processes may result in a lack of melanocytes, causing hypopigmentation, or in defects or changes in melanin (reviewed by Lamoreux et al., 2010, and Yamaguchi & Hearing, 2014).”

“Experimental studies have demonstrated that mutations in EDA correlate with coat colour phenotype in mice [59,60]; this gene has been proposed as a pigmentation candidate gene showing positive signatures of selection in humans [61].”

“Many genes have been implicated in specific aspects of melanocyte ⁄ melanoblast proliferation ⁄ migration ⁄ differentiation, and more than 370 loci are identified in the mouse affecting pigmentation (Bennett and Lamoreux, 2003; Lamoreux et al., 2010; Montoliu et al., 2012).”

“(iii) Piebaldism, although it only refers to white patches determined by piebald gene loci, is always used to refer to all white spotting [23,38]; this spotting occurs when melanin is absent from some or all of the areas in which it is normally present and is sometimes classified as partial leucism.”

“Laboratory mice present a vast diversity in coat colour, and mutations that affect mouse coat colour were among the first mutant alleles studied (Lamoreux et al., 2010).”

“…melanoblasts (cell-autonomous) or in keratinocytes (cell non-autonomous) may affect melanoblast migration, as has been shown for Kit/Steel, Ednrb/Edn3, Rac1, Cdc42, Prex1 and fascin (Lamoreux et al., 2010; Li et al., 2011; Lindsay et al., 2011; Ma et al., 2013; Silvers, 1979; Woodham et al., 2017).”

“Taking into consideration the different reproductive performances among mouse strains, two colonies were included in the study: C57BL/6 inbred strain with low performance 13 and B6CF1 hybrids with high performance 14 .”

“This trait is controlled by the melanocortin 1 receptor ( MC1R ) and Agouti ( ASIP ) genes (Lamoreux et al., 2010), but similar colorations among individuals may also be conferred by different mutations within these genes (van Grouw, 2013; Grouw, 2017).”

“Yellow Sinclair swine thought to carry Mc1r or ASIP mutations are resistant to melanoma, in contrast to black animals of the same lineage.(36) Gray Lipizzaner horses which are null for the Mc1r antagonist ASIP have a higher incidence of melanoma than horses which carry functional ASIP, indicating that increased Mc1r s…”

“Les mutants Microphthalmia (Mitf), dominant white spotting (Kit), Steel (Kitl), Piebald (Ednrb) et lethal spotting (Edn3) ont permis d’identifier les gènes et les protéines essentiels à la première étape de migration des mélanoblastes, qui suit leur délamination à partir du tube neural [1].”

“MC1R is the receptor for α- melanocyte-stimulating hormone (MSH), which promotes melanocyte differentiation, melanin synthesis, and the switch from pheomelanin (red/yellow) to eumelanin (black/brown) synthesis [96].”

“In medical science it is known as Oculocutaneous Albinism type 4 (Lamoreux et al. 2010).”

“…pigment cells in the skin and iris are derived from the neural crest (Du Shane 1935; Rubin et al. 1986; Sturm and Larsson 2009), while RPE cells of the retina originate from the neuroectodermal sheath of the eyecup (Lamoreux et al. 2010; Schraermeyer and Heimann 1999; Sturm and Larsson 2009).”

“These aberrations may have genetic origins, or they may be the result of environmental pressures during embryological development (Bechtel 1978), such as poor nutrition or illness (Lamoreux et al. 2010; Hudon et al. 2013; Espinal et al. 2016).”

“We made an opportunistic collection of an individual of M. nigricans, andwe determined its leucistic condition, based on the color of the skin and the eyes of black color, according to Lamoreux et al. (2010) and Lucati and López-Baucells (2016).”

“Disruptions in the production, transport, or deposition of either pheomelanin or eumelanin leads to unusual coloration (Lamoreux et al. 2010).”

“…often called piebald marks, are caused by a mutation of one of several genes that affect development or function of melanocytes, resulting in a localized absence of melanin and, therefore, patches of white skin or fur (Davis 2007; Dessinioti et al. 2009; Lamoreux et al. 2010; Abreu et al. 2013).”

“Actualmente, con excepción de algunos modelos animales, como el ratón Mus musculus, donde se conoce la herencia de la pigmentación (Lamoreux et al., 2010), no existen estudios que sustenten una clasificación precisa y resulta poco práctico llevar a cabo pruebas genéticas o dar seguimiento a un…”

“This is because the embryonic origin of melanin pigments in the eyes differs from the rest of the body, with eye pigments primarily forming from the outer layer of the optic cup (Lamoreux et al. 2010).”

“…aberrations result from melanin mutations: (a) White Spotting, characterized by abnormalities in the development of melanin cells; (b) Dilution, denoting issues with melanin deposition into feathers; and (c) Mela-nism, arising from defects in the type of melanin produced (Lamoreux et al. 2010).”

“The coat color genes are the most important genetic factors (Silvers, 1979; Hirobe, 1992a; Barsh, 1996; Bennett and Lamoreux, 2003; Lamoreux et al., 2010; Ito and Wakamatsu, 2011).”

“The coat color genes are important genetic factors (Silvers, 1979; Hirobe, 1992a, 2011; Hirobe and Abe, 1999; Bennett and Lamoreux, 2003; Lamoreux et al., 2010).”

“Page 13 of 23 may also be nonadaptive and serve no function, or spot patterns could be affected by 282 pleiotropic selection on a gene that influences multiple traits (Lamoreux et al. 2010).”

“The interest in this trait has led to the identi fi cation of hundreds of loci and pathways involved in vertebrate pigmentation (Elkin et al. 2022; Hidalgo et al. 2022; Kelsh 2004; Lynn Lamoreux et al. 2010).”

“K E Y W O R D S coat color, depigmentation, fur color, leucism, mustelid T A X O N O M Y C L A S S I F I C A T I O N Zoology total body discoloration, but rarely is accompanied by hypopigmented eyes (Abreu et al., 2013; Lamoreux et al., 2010; Lucati & LópezBaucells, 2017).”

“The coat color genes are the most important genetic factors (Silvers, 1979; Hirobe, 1992; Hirobe and Abe, 1999; Bennett and Lamoreux, 2003; Lamoreux et al., 2010; Hirobe, 2011).”

“This condition is characterized by a lack of retinal and integumentary pigmentation that results in white or pinkish skin and red eyes due to blood vessels that can be observed through colorless tissue (Lamoreux et al. 2010; van Grouw 2021).”

“This abnormality is characterized by a lack of retinal and integumentary pigmentation that results in white or pinkish skin and red eyes (Lamoreux et al. 2010; Romero et al. 2018).”

“El leucismo se atribuye a un gen recesivo que determina el tono blanco en la piel, pelaje o plumaje; siendo éste un factor clave en la regulación de formación de la melanina (Lamoreux et al., 2010; Abreu et al., 2013).”

“Focusing on those, four major categories of colouration alterations can be distinguished (Lamoreux et al. 2010 (Aguillon & Shultz 2023).”

“Las anomalías en la coloración de la piel y el pelaje, sean totales o parciales, son causadas por defectos genéticos que resultan en hiper o hipopigmentación, dando lugar a anomalías genéticas, tales como albinismo, melanismo o leucismo (Lamoreux et al., 2010).”

“Colour of the hair, skin and eyes in mammals is controlled by the amount of melanin production (Lamoreux et al. 2010; Lin and Fisher 2007), and anomalies in the typical colour for a given species can result from heritable genetic mutations (Shihlomule et al. 2024).”

“Numerous coat color genes are involved in regulating the development of mouse melanocytes (Takeuchi, 1968; Silvers, 1979; Hirobe, 1992a, 1995; Hirobe and Abe, 1999; Bennett and Lamoreux, 2003; Lamoreux et al., 2010; Hirobe, 2011).”