Genetic loci that regulate healing and regeneration in LG/J and SM/J mice

MRL mice display unusual healing properties. When MRL ear pinnae are hole punched, the holes close completely without scarring, with regrowth of cartilage and reappearance of both hair follicles and sebaceous glands. Studies using (MRL/lpr × C57BL/6)F₂ and backcross mice first showed that this phenomenon was genetically determined and that multiple loci contributed to this quantitative trait. The lpr mutation itself, however, was not one of them. In the present study we examined the genetic basis of healing in the Large (LG/J) mouse strain, a parent of the MRL mouse and a strain that shows the same healing phenotype. LG/J mice were crossed with Small (SM/J) mice and the F₂ population was scored for healing and their genotypes determined at more than 200 polymorphic markers. As we previously observed for MRL and (MRL × B6)F₂ mice, the wound-healing phenotype was sexually dimorphic, with female mice healing more quickly and more completely than male mice. We found quantitative trait loci (QTLs) on chromosomes (Chrs) 9, 10, 11, and 15. The heal QTLs on Chrs 11 and 15 were linked to differential healing primarily in male animals, whereas QTLs on Chrs 9 and 10 were not sexually dimorphic. A comparison of loci identified in previous crosses with those in the present report using LG/J × SM/J showed that loci on Chrs 9, 11, and 15 colocalized with those seen in previous MRL crosses, whereas the locus on Chr 10 was not seen before and is contributed by SM/J.     

Genomic analysis of the appearance of testicular oocytes in MRL/MpJ mice

Mammals produce sperm or oocytes depending on their sex; however, newborn MRL/MpJ (MRL) male mice produce oocytes within their testes. We previously reported that one of the genes responsible for this phenotype is present on the MRL-type Y chromosome (Y^MRL), and that multiple genes, probably autosomal, are also required for the development of this phenotype. In this study we focused on the autosomal genes and examined their relationship with this phenotype by analyzing the progeny from crosses between MRL mice and other strains. We first observed the male F1 progeny from the crosses between female A/J, C57BL/6 (B6), BALB/c, C3H/He, or DBA/2 mice and male MRL mice, and two consomic strains, male B6-Y^MRL and MRL-Y^B6. Testicular oocytes that were morphologically similar to those of MRL mice were detected in all mouse strains except BALBMRLF1; however, the incidence of testicular oocytes was significantly lower than that in MRL mice. The appearance of testicular oocytes in MRL-Y^B6 mice indicates that this phenotype is strongly affected by genomic factors present on autosomes, and that there is at least one other causative gene on the MRL-type autosomes (MRL testicular oocyte production, mtop) other than that on Y^MRL. Furthermore, a quantitative trait locus (QTL) analysis using N2 backcross progeny from crosses between female MRLB6F1 and male MRL mice revealed the presence of susceptibility loci for the appearance of testicular oocytes at 8–17 cM on Chr 15. These findings demonstrate that the appearance of testicular oocytes is regulated by the genetic factors on Chr 15 and on Y^MRL.

     

Communal Nesting among Genetically Similar House Mice

From March to October 1986, 35 house mice, Mus domesticus, were fitted with radio-transmitters and tracked in and around a Colorado feed shed for an average of 5 (range 2 to 17) days. 5 of 36 simultaneously tracked pairs of lactating females used identical nesting sites. Genotypic similarity at 5 enzyme loci, assayed from biopsies of blood and toes, indicated that these females were more genetically alike than would be expected if pairing occurred randomly among females. We posit that female house mice recognize and preferentially form communal nests with close relatives. Aside from the communally nesting females, minimal overlap occurred among home ranges of lactating females. Only 4 of 10 adult male home ranges appreciably overlapped female home ranges. The home ranges of these 4 males overlapped less than the other adult male home ranges suggesting that males defend one or more females for access to mating. The possibility that communally nesting females are nursing each other's pups is discussed.     

THE GENETICS OF AN ISOLATING MECHANISM BETWEEN TWO SIBLING SPECIES OF DROSOPHILA

Matings between Drosophila simulans females and males of the sibling species D. mauritiana are of abnormally short duration. These rapid matings interrupt the transfer of sperm, leading to substantial reproductive isolation in interspecific as compared to intraspecific copulations. Genetic analysis of this behavior shows that it is influenced much more by the male than the female genotype, with genes from D. simulans being dominant. In males, shortened copulation is caused by interspecific divergence at a minimum of three loci, with one gene on each of the major chromosomes. This is an underestimate of the true number of loci affecting the trait, which could be much larger. The two autosomes have the largest effect, whereas that of the X chromosome is much smaller. The genetic architecture of copulation duration and the larger effect of male than female genotype suggest that females can detect and discriminate against differences in male genitalia.     

The relationship between plasma fibronectin levels and autoimmune disease activity in MRL/l mice

Plasma fibronectin levels increased significantly over time in MRL/l mice with progressive autoimmune disease. At 100 and 120 days of age both male and female MRL/l mice exhibited significantly higher fibronectin (Fn) levels than the more resistant MRL/l controls. Male mice at early time points had Fn levels no greater than controls due perhaps to the later onset of disease in MRL/l males. In contrast, female MRL/l mice, when compared with MRL/n controls, had higher Fn levels from 40 days of age. The proteinuria in these animals was also above MRL/n controls from the first time point taken (Day 40). In a temporal study with female MRL/l mice, Fn levels peaked at age 120 days and reflected the pattern of the survival curve, indicating that plasma Fn levels have an association with disease activity.     

Influence of Adult Size on Mate Choice in the Solitary and Gregarious Parasitoids, Cotesia marginiventris and Cotesia flavipes

Female and male mate choice in relation to adult size were examined for the solitary and gregarious parasitoids, Cotesia marginiventris (Cresson) and Cotesia flavipes Cameron, respectively. In addition, male precopulatory behaviors were observed for evidence of male competition or a large-male advantage in mate acquisition. Male parasitoids are not known to offer female mates direct benefits, but females that mate high quality males may obtain indirect benefits, such as offspring that are more successful in obtaining mates. Female choice experiments for C. marginiventris found that large males approached females first more frequently than small males, and that females mated large males significantly more often than small males. Male choice experiments for C. marginiventris did not demonstrate a male preference for female size. In contrast, female choice experiments with C. flavipes found that females mated equally with large or small males, while male choice experiments showed that males attempted copulation and mated more frequently with smaller females. Male competition was not observed in the gregarious species C. flavipes, but competition in this gregarious parasitoid could be moderated by dispersal.     

The effect of thymectomy on lupus-prone mice

The effect of neonatal thymectomy on the induction and/or modification of murine SLE disease was examined in several representative groups of mice with early-life SLE (MRL/Mp-lpr/lpr females, BXSB males, (NZB X W)F1 females, (NZW X BXSB)F1 males and females), late-life SLE (MRL/Mp-+/+ and BXSB females), and normal strains (BALB/c and C57BL/6 females). Our results indicated that thymectomy prevented disease only in the MRL/Mp-lpr/lpr SLE mice, and that this effect diminished as thymectomy was delayed beyond 3 wk post-natally. In the other SLE mice studied, neonatal thymectomy did not modify disease symptoms to any significant degree. Moreover, depletion of mature T cells from donor BXSB male bone marrow did not affect the expression of early-life SLE in thymectomized BXSB female recipients. Neonatal thymectomy did not induce SLE in normal mice. Of note, neonatal thymectomy did not completely deplete the Thy-1.2+ cell population, i.e., 10 to 15% remained in the spleens of the thymectomized mice. This incomplete T cell depletion, together with the previously demonstrated dependence on and hyperresponsiveness of BXSB and (NZB X W)F1 B cells to T helper cell-derived accessory signals, cast doubts on earlier conclusions that B cells from some SLE mice can autonomously proliferate and differentiate to autoantibody-secreting cells. It seems more appropriate to conclude that B cells from the various SLE mice vary in their degree of response to, and production of, T cell-derived helper signals, and thus in their expression of B cell hyperactivity and disease.     

Genomic analysis of the appearance of testicular oocytes in MRL/MpJ mice

Mammals produce sperm or oocytes depending on their sex; however, newborn MRL/MpJ (MRL) male mice produce oocytes within their testes. We previously reported that one of the genes responsible for this phenotype is present on the MRL-type Y chromosome (Y^MRL), and that multiple genes, probably autosomal, are also required for the development of this phenotype. In this study we focused on the autosomal genes and examined their relationship with this phenotype by analyzing the progeny from crosses between MRL mice and other strains. We first observed the male F1 progeny from the crosses between female A/J, C57BL/6 (B6), BALB/c, C3H/He, or DBA/2 mice and male MRL mice, and two consomic strains, male B6-Y^MRL and MRL-Y^B6. Testicular oocytes that were morphologically similar to those of MRL mice were detected in all mouse strains except BALBMRLF1; however, the incidence of testicular oocytes was significantly lower than that in MRL mice. The appearance of testicular oocytes in MRL-Y^B6 mice indicates that this phenotype is strongly affected by genomic factors present on autosomes, and that there is at least one other causative gene on the MRL-type autosomes (MRL testicular oocyte production, mtop) other than that on Y^MRL. Furthermore, a quantitative trait locus (QTL) analysis using N2 backcross progeny from crosses between female MRLB6F1 and male MRL mice revealed the presence of susceptibility loci for the appearance of testicular oocytes at 8?C17?cM on Chr 15. These findings demonstrate that the appearance of testicular oocytes is regulated by the genetic factors on Chr 15 and on Y^MRL.     

Do male house mice (Mus musculus) discriminate between females that differ in nutritional status?

Most studies of mate choice have focused on female preference for male traits because it is generally assumed that since males provide less parental investment they are not choosy. However, if males suffer missed opportunity costs by mating with lower quality females, selection should favor males with the ability to discriminate among females. We tested the hypothesis that male house mice (Mus musculus) discriminate between females that differ in nutritional status (non-food-deprived versus food-deprived). We recorded the time males spent investigating either type of female and used that to determine preference (spending ≥55% of their total investigation time with one female). We also examined the effects of female nutritional status and female preference status (preferred versus non-preferred) on the reproductive success of males. Males did not display a preference for non-food-deprived females nor did their reproductive success vary with nutritional status or preference status of females. Interestingly, males spent more time investigating females that were closest to the male's own weight. In addition, pairs that were closer in weight were more likely to produce a litter. These results suggest that male house mice are capable of discriminating among females and that such discrimination may influence their reproductive success.     

SALIVARY ANDROGEN-BINDING PROTEIN (ABP) MEDIATES SEXUAL ISOLATION IN MUS MUSCULUS

We wanted to determine whether the microevolution of the mouse salivary androgen-binding protein (ABP) Alpha subunit gene (Abpa) could mediate sexual selection and thereby have a potential role in maintaining gene pool integrity where radiating mouse subspecies make secondary contact. This hypothesis is based upon previous work in this laboratory, which has shown that each subspecies apparently has its own allele and that these alleles have a 25-fold excess of nonsynonymous/synonymous base substitutions compared to an average protein under purifying selection. We provide direct evidence for ABP-assortative mate selection in a laboratory setting: Mus musculus domesticus and M. m. musculus female mice recognize and discriminate between the territories of male mice that essentially differ solely in their Abpa genotype and, when the males are present, the female prefers to mate with the one of her own ABP type. The observation that females could differentiate between the territories of the two males when those mice were absent suggests that the males marked their territories with ABP. In this study, we also detected ABP on the pelts of male mice and in their environment. It is likely that the animals apply the protein to their pelts by licking and that it is then deposited in their surroundings. We suggest that females of the two subspecies are able to discriminate between males of those subspecies on the basis of this protein molecule. Mouse salivary ABP might present a worthwhile system with which to study a prezygotic isolation mechanism in a mammal.     

Growth and survivorship as proximate causes of sexual size dimorphism in peninsula dragon lizards Ctenophorus fionni

Males and females differ in body size in many animals, but the direction and extent of this sexual size dimorphism (SSD) varies widely. Males are larger than females in most lizards of the iguanian clade, which includes dragon lizards (Agamidae). I tested whether the male larger pattern of SSD in the peninsula dragon lizard, Ctenophorus fionni, is a result of sexual selection for large male size or relatively higher mortality among females. Data on growth and survivorship were collected from wild lizards during 1991–1994. The likelihood of differential predation between males and females was assessed by exposing pairs of male and female lizards to a predator in captivity, and by comparing the frequency of tail damage in wild‐caught males and females. Male and female C. fionni grew at the same rate, but males grew for longer than females and reached a larger asymptotic size (87 mm vs. 78 mm). Large males were under‐represented in the population because they suffered higher mortality than females. Predation may account for some of this male‐biased mortality. The male‐biased SSD in C. fionni resulted from differences in growth pattern between the sexes. The male‐biased SSD was not the result of proximate factors reducing female body size. Indeed SSD in this species remained male‐biased despite high mortality among large males. SSD in C. fionni is consistent with the ultimate explanation of sexual selection for large body size in males.     

Potential contribution of prenatal estrogens to the sexual differentiation of mate preferences in mice

The neural mechanisms controlling sexual behavior are sexually differentiated by perinatal actions of gonadal hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estrogens, that exposure to prenatal estrogens completely defeminized their potential to show lordosis behavior in adulthood. Therefore, we determined here whether mate preferences were also affected in female AFP-KO mice. We observed a robust preference for an estrous female over an intact male in female AFP-KO mice, which were ovariectomized in adulthood and subsequently treated with estradiol and progesterone, whereas similarly treated WT females preferred the intact male over the estrous female. Gonadally intact WT males preferred the estrous female over the male, but only when visual cues were blocked by placing stimulus animals behind opaque partitions. Furthermore, when given the choice between an intact male and a castrated male, WT females preferred the intact male, whereas AFP-KO females showed no preference. Finally when given the choice between an estrous female and an ovariectomized female, WT males preferred the estrous female whereas AFP-KO females preferred the ovariectomized female or showed no preference depending on whether they could see the stimulus animals or not. Taken together, when AFP-KO females are tested under estrous conditions, they do not show any male-directed preferences, indicating a reduced sexual motivation to seek out the male in these females. However, they do not completely resemble males in their mate preferences suggesting that the male-typical pattern of mate preferences is not solely organized by prenatal estrogens.     

Effects of feeding endophyte-infected tall fescue seed on the reproductive performance in male and female CD-1 mice by combination crosses

The present study was undertaken to assess the effects of endophyte-infected Acremonium coenophialum tall fescue (KY 31) seed (80% infected) on the reproductive performance of male and female CD-1 mice by combination crosses. Forty-eight male and 48 female 30-d-old mice were randomly allocated to two diet treatments. Twenty-four males and 24 females were fed Diet 1, consisting of 50% non-infected fescue and 50% mouse chow; the remaining animals were fed Diet 2, containing 50% infected fescue. At the end of 50 d, the animals were paired in groups (n = 12) as follows: 1) Diet 1 males and females; 2) Diet 2 males and Diet 1 females; 3) Diet 1 males and Diet 2 females; and 4) Diet 2 males and females. The pairs were maintained on the diets of their female partners and were allowed to cohabitate for 96 h. After this period the males were removed and the females were carried to term. Pregnancy rates among the four treatment groups were 100, 83.3, 75.0 and 54.5%, respectively. Similarly, the average number of pups born per litter among the four groups were 11.5, 8.0, 9.7, and 7.5, respectively. Also, the weights (grams) of pups born per litter were 17.5, 12.6, 12.4, and 9.8, respectively. The results point out that the reproductive capacity of both male and female mice are affected (P < 0.05) by the ingestion of endophyte-infected fescue seeds. Such negative effects were more severe in the female than the male (P < 0.05).     

Is the Setal Patch on the Chelae of Hemigrapsus takanoi and Hemigrapsus sinensis (Crustacea,Brachyura, Varunidae) Advantageous in Fighting and Mating?

Many animals have unique morphological characters that function in social behavior. Sexual selection can affect the expression of such traits in males and females, leading to sexual dimorphism. We investigated the social function of setal patches on the chelae of two species of varunid crabs, one in which males, but not females, have setal patches (Hemigrapsus takanoi), and one in which both sexes have setal patches (Hemigrapsus sinensis). We experimentally removed setal patches and compared fighting and mating behavior of individuals with and without setal patches. In H. sinensis, males with setal patches removed were inferior fighters compared to intact males. In male H. takanoi and female H. sinensis, setal removal did not influence the outcome of fights. In mating, males lacking setal patches had a similar ability to copulate with females as intact males in both species. However, male H. takanoi with their setae removed tended to take more time to initiate copulation than did intact males. When females were given the opportunity to choose intact males or males without setal patches, females of H. takanoi did not discriminate between the two. Female H. sinensis, however, copulated with intact males more frequently compared to males lacking setal patches. Male H. sinensis showed no preferences for the presence of setal patches or the body size of females. Thus, our results indicate that setal patches have a social function in male H. takanoi and male H. sinensis, but not in female H. sinensis, suggesting that the setal patches of male crabs are a sexually selected trait in both species. However, the social function of male setal patches was more prominent in the species in which both sexes possess setal patches than in the species in which only males bear setal patches.     

Epimorphic regeneration in mice is p53-independent

The process of regeneration is most readily studied in species of sponge, hydra, planarian, and salamander (i.e., newt and axolotl). The closure of MRL mouse ear pinna through-and-through holes provides a model of unusual wound healing/regeneration in which a blastema-like structure closes the ear hole and cartilage and hair follicles are replaced. Recent studies, based on a broad level of DNA damage and a cell cycle pattern of G2/M "arrest," showed that p21^Cip1/Waf1 was missing from the MRL mouse ear and that a p21-null mouse could close its ear holes. Given the p53/p21 axis of control of DNA damage, cell cycle arrest, apoptosis, and senescence, we tested the role of p53 in the ear hole regenerative response. Using backcross mice, we found that loss of p53 in MRL mice did not show reduced healing. Furthermore, cross sections of MRL.p53^-/- mouse ears at 6 weeks post-injury showed an increased level of adipocytes and chondrocytes in the region of healing whereas MRL or p21^-/- mice show chondrogenesis alone in this same region, though at later time points. In addition, we also investigated other cell cycle-related mutant mice to determine how p21 was being regulated. We demonstrate that p16 and Gadd45 null mice show little healing capacity. Interestingly, a partial healing phenotype in mice with a dual Tgfb/Rag2 knockout mutation was seen. These data demonstrate an independence of p53 signaling for mouse appendage regeneration and suggest that the role of p21 in this process is possibly through the abrogation of the Tgfb/Smad pathway.     

The influence of females on male territorial dominance and female preference in dwelling place in laboratory mice

The influence of female mice (Mus musculus) on intermale aggression and the female choice between dominant and subordinate males were tested. Normal male mice were paired with a castrated male or a female. Two pairs of the same kind were housed together after acclimation for 3 days in half (home cage) of the apparatus, which was composed of eight cages connected by tunnels. One of the two normal males became dominant. The dominant males became more aggressive in the presence of females than in the presence of castrated males. The two normal males dwelt in their own home cages. The two females dwelt together and preferred to dwell in the home cages of the dominant male. The two castrated males dwelt together and seemed to decide their dwelling cage more freely than the subordinate normal male. Received: August 20, 1999 / Accepted: December 6, 1999     

Male Ornamentation in a Sex‐Role Reversed Pipefish Corythoichthys haematopterus

Sexual selection theory predicts that mating competition in sex‐role reversed animals acts more strongly on females than males and consequently females are expected to develop secondary sexual traits. However, in a sex‐role reversed pipefish Corythoichthys haematopterus (family: Syngnathidae), only males develop an ornamental trait on the thorax, consisting of approx. 3–5 speckles alternated by lateral stripes of brilliant light blue and orange. To understand the function of this male ornament, we examined whether the presence of females affects the expression of this trait, and whether the expression of this trait depends on the male’s physical condition. Individual males were reared in a tank for a month in four different conditions: in high or low food supply and in the presence or absence of a female. After 1 mo, males in better condition expressed larger and deeper blue and yellow speckles, and males maintained with a female expressed larger and deeper blue speckles than solely reared males. These results indicated that the male ornament functions as a signal conveying information on the phenotypic quality of its holder and that females are potential receivers of this signal. Because C. haematopterus exhibits strict monogamy and competition for a mate occurs only among females, we concluded that the male ornament is not displayed in the context of mating competition but rather it is used as a cue for partner recognition to maintain pair bond.     

The influence of urine from asymptotic laboratory populations on sexual maturation in prairie deermice

Male and female prairie deermice housed singly from weaning (21 days) until 40 days of age had urine from one of the following sources applied daily to their nostrils: sexually mature laboratory population males or females, and sexually mature breeder males or females from our laboratory colony. Other males and females were treated with water. Records were obtained of the weights of the tests, seminal vesicles and bacula of males and the ovaries and uteri of females at 40 days of age. The major results of this study were as follow: Female urine from sexually mature and inhibited population or isolated mice stimulated the development of the male reproductive organs significantly more than water or male urine. Male urine applied to young males did not differentially affect the weights of their reproductive organs compared with water and thus showed no inhibition effects. The reproductive organs of females treated with male urine did not differ significantly in weight from those of females treated with female urine. Females treated with water developed significantly larger uteri than those treated with urine from sexually mature population females (P≤0.02), inhibited population females (P<0.001) and inhibited population males (P<0.007).     

Nucleoside-specific suppression in MRL/MP +/+ mice

The induction of nucleoside-specific nonresponsiveness was further studied in the autoimmune strain MRL/MP +/+ (MRL/n). Experiments were undertaken to determine (i) whether nucleoside-conjugated spleen cells are able to induce specific nonresponsiveness to T-dependent nucleoside antigens in MRL/n mice, and (ii) whether periodic treatment with nucleoside-conjugated spleen cells would retard the development of spontaneous anti-DNA antibodies and associated indicators of autoimmunity. The results show that nonresponsiveness to nucleoside antigens is inducable in male, but not in female, MRL/n mice. Nonresponsiveness in male MRL/n was transferable and mediated by T cells. Treatment of male MRL/n mice with nucleoside-conjugated spleen cells (NSC) appeared to attenuate the progress of autoimmune symptoms in experimental animals. These results are discussed in the context of recent studies exploring the etiology of autoantibody production and the loss of self-tolerance in murine models of autoimmunity.     

Frequent Failure of Male Monopolization Strategies as a Cost of Female Choice in the Black Widow Spider Latrodectus tredecimguttatus

In many mating systems, males strive for securing paternity through monopolizing females. As male monopolization attempts often contradict female interests, this conflict may fuel an evolutionary arms race. In the widow spider genus Latrodectus, females are commonly polyandrous, whereas males are monogynous, hence restricted to mate with a single female, making paternity protection particularly important. Potential mating plugs (specialized embolus sclerites of male copulatory organs) have been discovered in the complex female genital tracts of several Latrodectus species. In this study, we investigated mating strategies in the Mediterranean black widow spider Latrodectus tredecimguttatus and tested the adaptive value of female attacks against male monopolization efforts. In a double mating experiment, we manipulated the number of insertions (=copulations) for first and second males to assess female behaviour and male embolus sclerite placement success. Our results indicate that first males′ embolus sclerites inside the females′ sperm stores physically block sclerites of subsequent males. While female attacks did not affect the deposition of potential mating plugs, they significantly reduced copulation duration. Irrespective of female aggression, male sclerite placement failure occurred frequently, but large males were more successful than smaller competitors. We suggest that the complex genital morphology in both sexes may have co‐evolved antagonistically and female morphology could serve to favour large males for fertilization.