Variation of coat color in house mice throughout Asia

Coat color variation due to melanin pigment synthesis in house mice Mus musculus in Asia is described and found to be consistent with Gloger's rule, which states that individuals of endothermic animals are darker in humid habitats than those in drier habitats. Three properties of coat color (hue, value and chroma) were measured, and a lightness variable was derived from a principal components analysis using 428 skin specimens representing three subspecies from 85 localities. Dorsal coat color ranged from yellow through brown to black, whereas ventral coat color ranged from white to black. Dorsal coat color varied less than the ventral color. In our samples, the variation in coat color in natural populations was far less than that observed in the laboratory. We found a significant correlation between the lightness variable of dorsal coat color and precipitation. Dark coat color was observed in more humid and closed habitats (darker background color), and pale coat color in drier, more open habitats (lighter background color). This result might imply the role of concealment as a selective force affecting dorsal coat color that was observed in house mice. We also discussed other selective forces that could affect the coat color variation in house mice, such as resistance to bacterial degradation and thermoregulation. In addition, the color spectra of the dorsal pelage among the three subspecies were different, the major distinction being the environmental background color of the habitats in which they are distributed.     

Development of a highly fecund inbred strain of mice

A highly fecund inbred mouse line has been established from the Quackenbush Swiss (QS) outbred strain by full-sib inbreeding combined with selection for high number of pups born alive (NBA) and low interlitter interval (ILI). After more than 50 generations of inbreeding and selection, this line, named QSi5, has an NBA of 13.4 and an ILI of 29 days, averaged over the first four parities, and a total productivity of 50.7 NBA. With its exceptional reproductive performance, this line will be very useful in the creation of resources (including advanced intercross lines) for analysis of quantitative trait loci for a wide range of traits, and for the cost-effective creation of congenic lines.     

The genetics of adaptive coat color in gophers: coding variation at Mc1r is not responsible for dorsal color differences

The genetics of adaptation is a key problem in evolutionary biology. Pocket gophers of the species Thomomys bottae provide one of the most striking examples of coat color variation in mammals. Dorsal pelage color is strongly correlated with soil color across the range of the species, presumably reflecting the selective pressure exerted by predation. To investigate the genetic basis of coat color variation in T. bottae, we cloned and sequenced the melanocortin-1 receptor locus (Mc1r), a candidate pigmentation gene, in 5 dark and 5 light populations of the species. Our results show that, in contrast to many other species of mammals and other vertebrates, coding variation at Mc1r is not the main determinant of coat color variation in T. bottae. These results demonstrate that similar phenotypic variation may have a different genetic basis among different mammalian species.     

Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site

For over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals. We found that individuals within strains are not isogenic, and there are differences in the levels of genetic variation that are explained by differences in the genetic distance from the colony nucleus. In addition, we employ a novel approach to mutation rate estimation based on the observed genetic variation and the expected site frequency spectrum at equilibrium, given a fully inbred breeding design. We find that it provides a reasonable per nucleotide mutation rate estimate when mice come from the colony nucleus (~7.9 × 10⁻⁹ in C3H/HeN), but substantially inflated estimates when mice come from production colonies.Subject terms: Evolutionary genetics, Evolutionary biology, Inbreeding, Genetic variation, Mutation     

Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory mice

Albinism, due to a lack of melanin pigment, is one of the oldest known mutations in mice. Tyrosinase (monophenol oxygenase, EC 1.14.18.1) is the first enzyme in the pathway for melanin synthesis, and the gene encoding this enzyme has been mapped to the mouse albino (c) locus. We have used mouse tyrosinase cDNA clones and genomic sequencing to study the albino mutation in laboratory mice. Within the tyrosinase gene coding sequences, a G to C transversion at nucleotide 308, causing a cysteine to serine mutation at amino acid 103, is sufficient to abrogate pigment production in transgenic mice. This same base pair change is fully conserved in classical albino strains of laboratory mice. These results indicate that a conserved mutation in the tyrosinase coding sequences is responsible for the classical albino mutation in laboratory mice, and also that most albino laboratory mouse strains have been derived from a common ancestor.     

Confidence intervals for the substitution number in the nucleotide substitution models

In the nucleotide substitution model for molecular evolution, a major task in the exploration of an evolutionary process is to estimate the substitution number per site of a protein or DNA sequence. The usual estimators are based on the observation of the difference proportion of the two nucleotide sequences. However, a more objective approach is to report a confidence interval with precision rather than only providing point estimators. The conventional confidence intervals used in the literature for the substitution number are constructed by the normal approximation. The performance and construction of confidence intervals for evolutionary models have not been much investigated in the literature. In this article, the performance of these conventional confidence intervals for one-parameter and two-parameter models are explored. Results show that the coverage probabilities of these intervals are unsatisfactory when the true substitution number is small. Since the substitution number may be small in many situations for an evolutionary process, the conventional confidence interval cannot provide accurate information for these cases. Improved confidence intervals for the one-parameter model with desirable coverage probability are proposed in this article. A numerical calculation shows the substantial improvement of the new confidence intervals over the conventional confidence intervals.     

Cyclic nucleotide levels in the brain of inbred mice in emotional stress exposure

The content of cAMP and cGMP in different brain regions was studied in C57Bl/6 and BALB/c mice at rest and upon exposure to emotional stress induced by open field technique. Interstrain differences in baseline nucleotide content, differences in nucleotide distribution in the brain regions and changes in their concentration after stress have been revealed.     

Coat color genetics of Peromyscus. I. Ashiness, an age-dependent coat color mutation in the deer mouse

Ashy deer mice (Peromyscus maniculatus) were first discovered about 1960 in a wild population from Oregon. Although indistinguishable from the wild type at weaning, ashy deer mice become progressively grayer with subsequent molts. The trait is inherited as an autosomal recessive and the symbol ahy is assigned for the locus. The trait is distinctly manifest by 6 months of age, at which time homozygotes have white hairs on the muzzle and at the base of the tail. The amount of white gradually increases with age, but development varies greatly among animals. Some become virtually all white by 18 months. Implants of melanocyte-stimulating hormone induced production of pigment in depigmented portions of the coat, indicating that viable melanocytes were present. The ashy deer mouse model may be useful for further study of melanocyte function.     

A new approach for estimating the efficiencies of the nucleotide substitution models

In this article, a new approach is presented for estimating the efficiencies of the nucleotide substitution models in a four-taxon case and then this approach is used to estimate the relative efficiencies of six substitution models under a wide variety of conditions. In this approach, efficiencies of the models are estimated by using a simple probability distribution theory. To assess the accuracy of the new approach, efficiencies of the models are also estimated by using the direct estimation method. Simulation results from the direct estimation method confirmed that the new approach is highly accurate. The success of the new approach opens a unique opportunity to develop analytical methods for estimating the relative efficiencies of the substitution models in a straightforward way.     

A missense mutation in the gene for melanocyte-stimulating hormone receptor (MCIR) is associated with the chestnut coat color in horses

The melanocyte-stimulating hormone receptor gene (MC1R) is the major candidate gene for the chestnut coat color in horses since it is assumed to be controlled by an allele at the extension locus. MC1R sequences were PCR amplified from chestnut (e/e) and non-chestnut (E/−) horses. A single-strand conformation polymorphism was found that showed a complete association to the chestnut coat color among 144 horses representing 12 breeds. Sequence analysis revealed a single missense mutation (83Ser → Phe) in the MC1R allele associated with the chestnut color. The substitution occurs in the second transmembrane region, which apparently plays a key role in the molecule since substitutions associated with coat color variants in mice and cattle as well as red hair and fair skin in humans are found in this part of the molecule. We propose that the now reported mutation is likely to be the causative mutation for the chestnut coat color. The polymorphism can be detected with a simple PCR-RFLP test, since the mutation creates a TaqI restriction site in the chestnut allele. Received: 20 May 1996 / Accepted: 31 July 1996     

Toxic effect of lead on fertility of inbred strain mice.

Males of inbred strains were orally given lead acetate water solution during 150 days. Changes were found in the structure of the seminiferous tubules and in spermatozoa. The pathological changes in Leydig cells brought about a decline in levels of androgens.     

Genotype-dependent participation of coat color gene loci in the behavioral traits of laboratory mice

To evaluate if loci responsible for coat color phenotypes contribute to behavioral characteristics, we specified novel gene loci associated with social exploratory behavior and examined the effects of the frequency of each allele at distinct loci on behavioral expression. We used the F2 generation, which arose from the mating of F1 mice obtained by interbreeding DBA/2 and ICR mice. Phenotypic analysis indicated that the agouti and albino loci affect behavioral traits. A genotype-based analysis revealed that novel exploratory activity was suppressed in a manner dependent on the frequency of the dominant wild-type allele at the agouti, but not albino, locus. The allele-dependent suppression was restricted to colored mice and was not seen in albino mice. The present results suggest that the agouti locus contributes to a particular behavioral trait in the presence of a wild-type allele at the albino locus, which encodes a structural gene for tyrosinase.     

A codon-based model of nucleotide substitution for protein-coding DNA sequences

A codon-based model for the evolution of protein-coding DNA sequences is presented for use in phylogenetic estimation. A Markov process is used to describe substitutions between codons. Transition/transversion rate bias and codon usage bias are allowed in the model, and selective restraints at the protein level are accommodated using physicochemical distances between the amino acids coded for by the codons. Analyses of two data sets suggest that the new codon-based model can provide a better fit to data than can nucleotide-based models and can produce more reliable estimates of certain biologically important measures such as the transition/transversion rate ratio and the synonymous/nonsynonymous substitution rate ratio.