scholarly journals Opposite Orientations of an Inverted Duplication and Allelic Variation at the Mouse agouti Locus

Genetics ◽  
1996 ◽  
Vol 144 (1) ◽  
pp. 265-277
Author(s):  
Yanru Chen ◽  
David M J Duhl ◽  
Gregory S Barsh
Keyword(s):  
Homologous Recombination ◽  
Allelic Variation ◽  
Inbred Strains ◽  
Mrna Isoforms ◽  
Pigment Synthesis ◽  
Agouti Locus ◽  
Agouti Protein ◽  
Hybridization Probes ◽  
Inverted Duplication ◽  
Untranslated Exon

Abstract The mouse agouti protein is a paracrine signaling molecule that causes yellow pigment synthesis. A pale ventral coloration distinguishes the light-bellied agouti (AW) from the agouti (A) allele, and is caused by expression of ventral-specific mRNA isoforms with a unique 5′ untranslated exon. Molecular cloning demonstrates this ventral-specific exon lies within a 3.1-kb element that is duplicated in the opposite orientation 15-kb upstream to produce an interrupted palindrome and that similarity between the duplicated elements has been maintained by gene conversion. Orientation of the palindrome is reversed in A compared to AW, which suggests that mutation from one allele to the other is caused by intrachromosomal homologous recombination mediated by sequences within the duplicated elements. Analysis of 15 inbred strains of laboratory and wild-derived mice with Southern hybridization probes and closely linked microsatellite markers suggests six haplotype groups: one typical for most strains that carry AW (129/SvJ, LP/J, CE/J, CAST/Ei), one typical for most strains that carry A (Balb/cJ, CBA/J, FVB/N, PERA/Rk, RBB/Dn); and four that are atypical (MOLC/Rk, MOLG/Dn, PERA/Ei, PERC/Ei, SPRET/Ei, RBA/Dn). Our results suggest a model for molecular evolution of the agouti locus in which homologous recombination can produce a reversible switch in allelic identity.

scholarly journals Allelic Variation Within the Emv-15 Locus Defines Genomic Sequences Closely Linked to the agouti Locus on Mouse Chromosome 2

Genetics ◽  
1987 ◽  
Vol 117 (1) ◽  
pp. 85-92
Author(s):  
Linda D Siracusa ◽  
Liane B Russell ◽  
Nancy A Jenkins ◽  
Neal G Copeland
Keyword(s):  
Coat Color ◽  
Allelic Variation ◽  
Close Linkage ◽  
Brown Pigment ◽  
Chromosome 2 ◽  
Pigment Synthesis ◽  
Agouti Locus ◽  
Mouse Sequence ◽  
Lethal Yellow ◽  
Mouse Chromosome 2

ABSTRACT Gene(s) at the agouti locus act within the microenvironment of the hair follicle to switch pigment synthesis in the melanocyte between eumelanin (black or brown pigment) and phaeomelanin (yellow pigment). Many phenotypic variants of this locus have been described. The mechanism(s) of gene action causing such variation in coat-color phenotype is not known. The close linkage of an endogenous ecotropic murine leukemia provirus, Emv-15, to the lethal yellow mutation of the agouti locus provides a means to molecularly access genes at or near the agouti locus. We have identified and used a unique mouse sequence flanking the Emv-15 provirus to define three alleles of the Emv-15 locus. We found a correlation between the presence of specific Emv-15 alleles and the origins of specific agouti locus mutations, confirming close linkage. However, we found some exceptions which suggest that the Emv-15 locus is closely linked to, but genetically separable from, the agouti locus.

scholarly journals The original pink-eyed dilution mutation (p) arose in Asiatic mice: implications for the H4 minor histocompatibility antigen, Myod1 regulation and the origin of inbred strains.

Genetics ◽  
1994 ◽  
Vol 138 (1) ◽  
pp. 203-211 ◽  
Author(s):  
M H Brilliant ◽  
A Ching ◽  
Y Nakatsu ◽  
E M Eicher
Keyword(s):  
Allelic Variation ◽  
Inbred Strains ◽  
Histocompatibility Antigen ◽  
Chromosome 7 ◽  
Minor Histocompatibility Antigen ◽  
Wild Mice ◽  
P Gene ◽  
The Difference ◽  
Pink Eyed Dilution ◽  
Common Laboratory

Abstract Allelic variation of the mouse pink-eyed dilution (p) gene in common laboratory strains and wild mice was examined by Southern blot and by polymerase chain reaction. In these assays the original p mutation allele found in strains SJL/J, 129/J, B10.129(21m), P/J and FS/Ei most closely matches an Asian Mus musculus allele, confirming anecdotal accounts of the Asian origin of this mutation. In contrast, the wild-type allele found in other common laboratory strains was apparently derived from Mus domesticus. Analysis of chromosome 7 loci both proximal and distal to the p locus demonstrates that strains SJL/J, 129/J, B10.129(21M), P/J and FS/Ei contain DNA segments of varying length derived from M. musculus. Strains 129/J and B10.129(21M) contain the largest segment of M. musculus-derived DNA (about 5 cM), including the loci Myod1, p, three clustered GABAA receptor subunit loci (Gabrg3, Gabra5 and Gabrb3), and Snrpn. The difference in the species origin of genes from this region of chromosome 7 may underlie the basis of the antigenicity of the minor histocompatibility antigen H4, defined by the strain B10.129(21M), and may account for the enhanced Myod1 activity observed in SJL/J mice.

scholarly journals INFLUENCE OF MATERNAL PHENOTYPE ON METABOLIC DIFFERENTIATION OF AGOUTI LOCUS MUTANTS IN THE MOUSE

Genetics ◽  
1978 ◽  
Vol 88 (3) ◽  
pp. 529-539
Author(s):  
George L Wolff
Keyword(s):  
Reciprocal Cross ◽  
Coat Color ◽  
Inbred Strains ◽  
Tumor Formation ◽  
Phenotypic Differentiation ◽  
Metabolic Characteristics ◽  
Agouti Locus ◽  
Uterine Environment ◽  
Strain Genome ◽  
Extensive Breeding

ABSTRACT The results of extensive breeding experiments indicate that the phenotypic differentiation of embryos carrying the viable yellow, Avy, or mottled, am, mutations is influenced to a major extent by the agouti locus genotype and the strain genome of the dam. The Avy/a and am/a genotypes are each expressed in a spectrum of coat color phenotypes. These can be grouped into two classes, mottled and pseudoagouti.—In a reciprocal cross of C57BL/6JNIcrWf and AM/Wf-am/am mice, 29.5% of the offspring of C57BL/6 dams were of the pseudoagouti phenotype, whereas no pseudoagouti offspring were produced by AM strain dams.—Mottled yellow Avy/a mice become obese and tumor formation is enhanced in these mice in comparison with the lean pseudoagouti Avy/a siblings.—In two different reciprocal crosses using four different inbred strains, the proportion of pseudoagouti Avy/a offspring differed according to the strain of the dam. Regardless of strain, mottled yellow Avy/a dams produced significantly fewer pseudoagouti Avy/a offspring than did black a/a dams.—The data suggest that metabolic differentiation of Avy/a zygotes into phenotypic classes with different susceptibilities to obesity and tumor formation is influenced to a considerable degree by the metabolic characteristics of the oviductal and uterine environment of the dam.

scholarly journals Molecular Markers for the agouti Coat Color Locus of the Mouse

Genetics ◽  
1987 ◽  
Vol 115 (4) ◽  
pp. 747-754
Author(s):  
Michael Lovett ◽  
Zai-yu Cheng ◽  
Estrella M Lamela ◽  
Tohru Yokoi ◽  
Charles J Epstein
Keyword(s):  
Molecular Markers ◽  
Dna Sequences ◽  
Coat Color ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Single Copy ◽  
Mouse Strains ◽  
Chromosome 2 ◽  
Agouti Locus ◽  
Lethal Yellow

ABSTRACT The agouti (a) coat color locus of the mouse acts within the microenvironment of the hair follicle to control the relative amount and distribution of yellow and black pigment in the coat hairs. Over 18 different mutations with complex dominance relationships have been described at this locus. The lethal yellow (Ay) mutation is the top dominant of this series and is uniquely associated with an endogenous provirus, Emv-15, in three highly inbred strains. However, we report here that it is unlikely that the provirus itself causes the Ay-associated alteration in coat color, since one strain of mice (YBR-Ay/a) lacks the provirus but still retains a yellow coat color. Using single-copy mouse DNA sequences from the regions flanking Emv-15 we have detected three patterns of restriction fragment length polymorphisms (RFLPs) within this region that can be used as molecular markers for different agouti locus alleles: a wild-type agouti (A) pattern, a pattern which generally cosegregates with the nonagouti (a) mutation, and a pattern which is specific to Emv-15. We have used these RFLPs and a panel of 28 recombinant inbred mouse strains to determine the genetic linkage of these sequences with the agouti locus and have found complete concordance between the two (95% confidence limit of 0.00 to 3.79 centimorgans). We have also physically mapped these sequences by in situ hybridization to band H1 of chromosome 2, thus directly confirming previous assignments of the location of the agouti locus.

scholarly journals Mapping of microsatellite loci and association of aorta atherosclerosis with LG VI markers in the rabbit

2001 ◽  
Vol 6 (1) ◽  
pp. 11-18 ◽  
Author(s):  
R. KORSTANJE ◽  
G. F. GILLISSEN ◽  
L. P. KODDE ◽  
M. DEN BIEMAN ◽  
A. LANKHORST ◽  
...  
Keyword(s):  
Linkage Group ◽  
Microsatellite Markers ◽  
Microsatellite Marker ◽  
Biochemical Marker ◽  
Allelic Variation ◽  
Dietary Cholesterol ◽  
Inbred Strains ◽  
Chromosome 1 ◽  
Group Vi ◽  
Nucleotide Database

Twenty-three rabbit microsatellites were extracted from the EMBL nucleotide database. Nine of these markers, together with nine earlier published microsatellite markers, were found to be polymorphic between the AX/JU and IIIVO/JU inbred strains. By using an F2 intercross we could integrate five markers into the rabbit linkage map. One anonymous microsatellite marker could be assigned to chromosome 1, and one microsatellite marker, located within the metallothionein-1 gene, could be added to linkage group VI (LG VI). Three microsatellite markers (one anonymous, one located within the PMP2 gene, and one located within the FABP6 gene) constitute a new linkage group (LG XI). We also measured the degree of dietary cholesterol-induced aorta atherosclerosis in the F2 animals. A significant cosegregation was found between the degree of aorta atherosclerosis and the allelic variation of the biochemical marker Est-2 on LG VI in male rabbits. This association was not found in female rabbits.

scholarly journals Genetics of plasma transferrins in the mouse

1960 ◽  
Vol 1 (3) ◽  
pp. 431-438 ◽  
Author(s):  
B. L. Cohen
Keyword(s):  
Gel Electrophoresis ◽  
Molecular Basis ◽  
Plasma Proteins ◽  
Inbred Strains ◽  
The Other ◽  
Starch Gel Electrophoresis ◽  
Widespread Distribution ◽  
Agouti Locus ◽  
Inbred Strains Of Mice ◽  
Starch Gel

1. The plasma proteins of six inbred strains of mice have been studied, using starch-gel electrophoresis.2. The existence of two alternative plasma transferrin (β-globulin) phenotypes has been demonstrated. Five of the strains have one of these and one strain has the other. Each of the two transferrin patterns comprises three (or possibly only two) electrophoretic bands. The two patterns differ in all of these bands.3. The two transferrin types recognized are determined by a pair of allelic, autosomal genes (designated TrfA and TrfB). The TrfA phenotype (CBA strain) is determined by the genotype TrfA/TrfA, and the TrfB phenotype (A, C57BL, JU, KL, RIII strains) by the genotype TrfB/TrfB. The phenotype TrfAB, of the heterozygote (genotype TrfA/TrfB), is distinguishable and shows four (or possibly only three) bands. In this way it closely resembles a mixture of equal parts of TrfA and TrfB plasma.4. No linkage was detected between the Trf locus and sex, the agouti locus or the haemoglobin locus.5. The possible molecular basis of the action of the transferrin alleles in the mouse, and the widespread distribution in mammals of polymorphism involving the transferrins, are discussed.

Identification and genetic monitoring of mouse inbred strains using biochemical polymorphisms

1977 ◽  
Vol 11 (4) ◽  
pp. 209-214 ◽  
Author(s):  
A. Groen
Keyword(s):  
The Netherlands ◽  
Allelic Variation ◽  
Inbred Strains ◽  
Genetic Monitoring ◽  
Unique Combination ◽  
Genetic Purity ◽  
Body Protein ◽  
Biochemical Polymorphisms ◽  
Routine Monitoring ◽  
Inbred Strains Of Mice

53 inbred strains and substrains of mice from 3 institutes in The Netherlands were examined at 12 chromosome loci coding body protein-polymorphism (Es-1, Es-2, Es-3, Es-S, Gpi-1, Hbb, Id-1, Ldr-1, Mpi-1, Mup-1, pgm-1, Trf). The allelic variation at 7 loci could be detected simultaneously. Within each institute most strains showed a unique combination of alleles at the 12 loci involved. Some nominally similar (sub)strains showed allelic divergence. One strain showed allelic variation at 4 loci. These findings emphasize the possibility and the necessity of monitoring the genetic purity of inbred strains of mice. A routine monitoring scheme using body protein-polymorphisms is proposed.

scholarly journals Physical and genetic characterization of a 75-kilobase deletion associated with al, a recessive lethal allele at the mouse agouti locus.

Genetics ◽  
1989 ◽  
Vol 121 (4) ◽  
pp. 811-818
Author(s):  
G S Barsh ◽  
C J Epstein
Keyword(s):  
Complex Structure ◽  
Secretory Protein ◽  
Intragenic Recombination ◽  
Recessive Lethal ◽  
Molecular Alterations ◽  
Agouti Locus ◽  
Weight Restriction ◽  
Hybridization Probes ◽  
Radiation Induced ◽  
Lethal Allele

Abstract The agouti locus (A) of the mouse determines the timing and type of pigment deposition in the growing hair bulb, and several alleles at this locus are lethal when homozygous. Apparent instances of intragenic recombination and complementation between different recessive lethal alleles have suggested that the locus has a complex structure. We have begun to investigate the molecular basis of agouti gene action and recessive lethality by using a series of genetically linked DNA probes and pulsed field gel electrophoresis to detect structural alterations in radiation-induced agouti mutations. Hybridization probes from the Src and Emv-15 loci do not reveal molecular alterations in DNA corresponding to the ae, ax, and al alleles, but a probe from the parotid secretory protein gene (Psp) detects a 75-kilobase (kb) deletion in DNA containing the non-agouti lethal allele (al). The deletion is defined by a 75-kb reduction in the size of BssHII, NotI, NruI and SacII high molecular weight restriction fragments detected with the Psp probe and is located between 25 kb and 575 kb from Psp coding sequences. Because the genetic distance between A and Emv-15 is much less than A and Psp, there may be a preferred site of recombination close to Psp, or suppression of recombination between A and Emv-15. The al deletion has allowed us to determine the genotype of mice heterozygous for different recessive lethal alleles. We find that three different recessive lethal complementation groups are present at the agouti locus, two of which are contained within the al deletion.

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