Genetic control of catalepsy in mice

Pinch-induced immobility (catalepsy) was studied in mice of 9 inbred strains. CBA mice were found to be different from those of other strains both by the highest percent of cataleptics (56%) and by the highest duration of immobility. The Mendelian analysis of predisposition to catalepsy was performed on CBA and AKR mice strains contrasting in this feature. Reciprocal F1 hybrids did not display any catalepsy. Manifestation of cataleptics in the F2 and in CBA x F2 backcrosses suggested that catalepsy was inherited as a recessive, monogenic, autosomal feature.     

Genetic control of glucuronidase in mice

Two electrophoretically distinct components of glucuronidase have been resolved in extracts of murine liver. A mutation which results in a ten-fold reduction in liver glucuronidase activity leads to a reduction in intensity of both components. Since the substrate dependencies of both mutant (gg) and wild-type (GG) glucuronidase have previously been shown to be identical, it is suggested that the mutation results in a decreased concentration of liver glucuronidase molecules. Furthermore, the anodal electrophoretic component is shown to be preferentially localized in lysosomes, while the cathodal component is primarily microsomal. The difference in mobility of the two components may reflect a difference in membranous elements attached to the extracted glucuronidase molecule.This paper was presented at a symposium entitled Genetic Control of Mammalian Metabolism held at The Jackson Laboratory, Bar Harbor, Maine, June 30–July 2, 1969. The symposium was supported in part by an allocation from NIH General Research Support Grant FR 05545 from the Division of Research Resources to The Jackson Laboratory.This investigation was supported by a grant from the Pharmaceutical Manufacturers Association Foundation.     

Genetic control of temperature preference in the nematode Caenorhabditis elegans

Animals modify behavioral outputs in response to environmental changes. C. elegans exhibits thermotaxis, where well-fed animals show attraction to their cultivation temperature on a thermal gradient without food. We show here that feeding-state-dependent modulation of thermotaxis is a powerful behavioral paradigm for elucidating the mechanism underlying neural plasticity, learning, and memory in higher animals. Starved experience alone could induce aversive response to cultivation temperature. Changing both cultivation temperature and feeding state simultaneously evoked transient attraction to or aversion to the previous cultivation temperature: recultivation of starved animals with food immediately induced attraction to the temperature associated with starvation, although the animals eventually exhibited thermotaxis to the new temperature associated with food. These results suggest that the change in feeding state quickly stimulates the switch between attraction and aversion for the temperature in memory and that the acquisition of new temperature memory establishes more slowly. We isolated aho (abnormal hunger orientation) mutants that are defective in starvation-induced cultivation-temperature avoidance. Some aho mutants responded normally to changes in feeding state with respect to locomotory activity, implying that the primary thermosensation followed by temperature memory formation remains normal and the modulatory aspect of thermotaxis is specifically impaired in these mutants.     

Genetic control of glucokinase activity in mice

Inbred strains of mice were surveyed for liver glucokinase activity. Mice of all strains studied could be distributed into three groups with high, intermediate, and low levels of enzyme activity. Genetic analysis using crosses and backcrosses with prototype high (C3H/HeJ) and low (RF/J) strains revealed that glucokinase activity was controlled by a single gene. The name glucokinase and gene symbol Gk are suggested for this gene. The Gk ^a allele designates the strain with high glucokinase activity, while Gk ^b represents the allele in the strain with the low enzyme activity. The interaction of fasting and diabetes on the activity of glucokinase in these two strains is described.Supported in part by United States Public Health Service Research Grant CA 05873 from the National Cancer Institute. The Jackson Laboratory is fully accredited by the American Association for the Accreditation of Laboratory Animal Care.     

Genetic control of ganglioside biosynthesis in mice

The enzymatic basis for the differences in hepatic ganglioside patterns in the mouse strains C57Bl/6 and Swiss White (SW) was investigated. SW has a “Swiss-type” ganglioside profile, expressing G_M1 ^? and G_D1a ^? in addition to G_M2 ^? as major hepatic gangliosides, whereas C57Bl/6 shows a “G_M2-type” profile, expressing only G_M2 ^? as the major hepatic ganglioside. The enzyme UDP-galactose:G_M2 ganglioside galactosyltransferase (G_M2-GalT), which catalyzes the synthesis of G_M1 ganglioside, showed a four- to fivefold elevation in intact and solubilized liver Golgi membrane fractions of the SW strain compared to C57Bl/6. Crosses between C57Bl/6 and SW produced an F₁ generation with a hepatic ganglioside and enzymatic phenotype intermediate between those of the two parental strains. All three genotypic groups show two forms of the Golgi apparatus enzyme with isoelectric points of 6.5–6.8 and 8.3–9.0. The simplest mode of action of genes which control the enzymatic phenotype that would be consistent with these findings are one or two structural genes or one or two cis-regulatory genes affecting the rate of enzyme synthesis.     

Genetic control of glucuronidase induction in mice

The β-glucuronidase activity of mouse kidney proximal tubule cells increases rapidly after administration of dihydrotestosterone. Several inbred mouse strains show an approximately fourfold greater response in enzyme activity than the majority of strains, although both groups have similar uninduced kidney glucuronidase activity. This difference is maintained throughout a three-week induction period. It is not accounted for by a difference in any of the physiological parameters (e.g. hypertrophy, inducer specificity, enzyme secretion) associated with enzyme induction. The difference is specific to glucuronidase; assays of other androgen-indueible enzymes showed no difference between the two groups. Induction does not involve a change in enzyme structure since basal and induced glucuronidase have identical thermal stability and immunochemical reactivity.Rates of enzyme synthesis were determined by assaying the incorporation of radiolabeled leucine into antibody-purified glucuronidase. The rate of enzyme synthesis increases after induction, and the more rapidly inducing strains have a correspondingly greater increase in the rate of enzyme synthesis.The inducibility difference between the two classes of inbred strains segregates as a single Mendelian trait in both backcross and F₂ progeny. Recombination studies with a coat color mutation closely linked to the enzyme structural gene and with a mutant of the enzyme structural gene altered in electrophoretic mobility showed that the inducibility gene, called Gur, maps in the region of the glucuronidase structural gene. Tests in heterozygotes showed that the Gur locus acts cis, affecting only the rate of synthesis of glucuronidase coded by the structural gene residing on the same chromosome.     

Oviposition preference for novel versus normal food resources in laboratory populations ofDrosophila melanogaster

Female fecundity, oviposition preference and specificity on one normal and two novel food media were assayed on four laboratory populations ofDrosophila melanogaster, revealing considerable among- and within-population variation in oviposition preference. Overall, there was a significant tendency of females to prefer novel media to their normal banana food as an oviposition substrate. Specificity in the populations was fairly high, implying that a large proportion of females tended to lay the majority of their eggs on the preferred medium. The results showed that oviposition preference for a given food medium could be affected by the alternative provided, and that, consequently, oviposition preference for a given food medium versus another cannot be predicted based upon a knowledge of what the preference for each of the two media was versus a common third medium. Specificity, on the other hand, was not significantly affected by the type of alternative food media provided in a given trial. Moreover, comparison of results from fecundity and oviposition preference assays also showed that the egg laying behaviour ofDrosophila females in response to different food media may be different in choice versus no-choice situations. Thus, a substrate on which fecundity is higher than on another, when assayed in a no-choice situation, may not be preferred over the other substrate when a choice between the two is provided to the ovipositing females. The latter two results point to possible complexity in the responses of females to various oviposition substrates based upon the overall setting of the assay, including the alternative substrates present for egg laying.     

Factors involved in herbivore food preference

Herbivore food preference can be measured either in terms of attractiveness or of edibility: these quantities are not necessarily correlated. The isopod Idotea baltica (Pallas) is attracted to large, tough, branched algae (perennials) while the amphipod Ampithoe valida (Smith) is attracted to softer, filamentous or bladed algae (ephemerals). Attractiveness for Ampithoe is related to the nutritive value of the algae; this is not so for Idotea, which responds more to algal morphology and availability. Idotea's mobility, possible susceptibility to fish predation, and preference for moderate wave exposures may select for a primary response to algae as habitat rather than as food source.     

Genetic control of scrapie and Creutzfeldt-Jakob disease in mice

Genetic control of experimental scrapie and Creutzfeldt-Jakob disease (CJD) was studied in inbred strains of mice by measuring the times from intracerebral inoculation with the agents to the onset of neurological dysfunction. Every strain of mice examined was susceptible to infection; however, a wide range of incubation times was found for both scrapie and CJD. New Zealand (NZ) mice, which eventually develop an autoimmune disorder, were inoculated intracerebrally with 10(6) ID50 units of the scrapie agent in a Chandler isolate. NZW mice showed incubation periods of less than 95 days; this is the shortest period recorded for any murine host with scrapie. In NZB and NZB X W F1 mice, the incubation periods were approximately 130 days and were similar to those in BALB/c and C57BL mice. Male and female NZ mice exhibited scrapie incubation periods of the same length. Similar results were obtained when B10.Q and C57BL/6J mice were inoculated intracerebrally with 10(4) ID50 units of the CJD agent in a K.Fu. isolate. These observations define a genetic locus or loci controlling the length of scrapie and CJD incubation periods; alleles coding for longer incubation times appear to be autosomal dominant. When congenic mice with a C57BL/10J background differing only in their H-2 haplotypes were studied, the results showed that the D subregion of the H-2 complex played a central role in controlling the length of the CJD incubation period. The q allele at the D subregion resulted in shorter incubation times, whereas the d allele resulted in long incubation times. The p, s, b, and k alleles gave intermediate incubation times. We propose the symbol PID-1 for designating this genetic locus which is located within the D subregion of the major histocompatibility (H-2) complex on murine chromosome 17. In addition, observations on congenic mice provide evidence for the influence of sex on CJD incubation periods. In some strains of inbred mice, males showed significantly shorter incubation periods compared with those for females with experimental CJD. These studies with inbred mice have defined previously unrecognized genes that control the length of scrapie and CJD incubation periods.     

Genetic control of hormone-induced ovulation rate in mice.

The nature of genetic differences in ovarian responsiveness to gonadotropins was examined in mouse strains and subspecies. Hormone-induced ovulation rate (HIOR) differed 5-fold between Mus musculus strains A/J (10.3 +/- 1.6 eggs in cumulus) and C57BL/6J (B6) (47.3 +/- 2.5 eggs in cumulus), and 6-fold among Mus spretus lines and crosses. Subspecies differed up to 10-fold in HIOR (Mus spretus/Ros: 4.8 +/- 1.0 eggs in cumulus versus B6). An additional experiment examined the genetics of HIOR in crosses. The number of eggs ovulated in response to equine chorionic gonadotropin (CG)/human CG averaged 8.4 +/- 0.9 in A/J, 40.7 +/- 1.7 in B6, 33.9 +/- 1.6 in B6AF1, and 20.2 +/- 0.3 in (B6xA)xA backcrosses. The 5-fold genetic differences in hormone-induced ovulation rate between Mus musculus strains A/J and B6 segregated in backcrosses as though they were controlled by the action of approximately 3 loci with major effects. This study demonstrates genetic variation in HIOR both within and between mouse subspecies, and provides confirmation that genetic differences are a major source of variation in the regulation of ovarian responsiveness to gonadotropins.     

Genetic control of retroviral disease in aging wild mice

Different populations of wild mice (Mus musculus domesticus) in Los Angeles and Ventura Counties were observed over their lifespan in captivity for expression of infectious murine leukemia virus (MuLV) and murine mammary tumor virus (MMTV) and for the occurrence of cancer and other diseases. In most populations of feral mice these indigenous retroviruses were infrequently expressed and cancer seldom occurred until later in life (>2 years old). MMTV was found in the milk of about 50% of wild mice, but was associated with only a low incidence (>1%) of breast cancer after one year of age. By contrast, in several populations, most notably at a squab farm near Lake Casitas (LC), infectious MuLV acquired at birth via milk was highly prevalent, and the infected mice were prone to leukemia and a lower motor neuron paralytic disease after one year of age. These two diseases were both caused by the same infectious (ecotropic)strain of MuLV and were the principal cause of premature death in these aging LC mice. A dominant gene called FV-4^R restricting the infection with ecotropic MuLV was found segregating in LC mice. Mice inheriting this FV-4^R allele were resistant to the ecotropic MuLV associated lymphoma and paralysis. The FV-4^R allele represents a defective endogenous MuLV provirus DNA segment that expresses an ecotropic MuLV envelope-related glycoprotein (gp70) on the cell surface. This FV-4^R encoded gp70 presumably occupies the receptor for ecotropic MuLV and blocks entry of the virus. The FV-4^R gene was probably acquired by the naturally occurring crossbreeding of LC feral mice with another species of feral mice (Mus castaneus) from Southeast Asia. The FV-4^R gp70 does not block entry of the amphotropic MuLV that uses a separate cell surface receptor. Therefore LC mice continued to be susceptible to the highly prevalent but weakly lymphogenic and nonparalytogenic amphotropic strain of MuLV. The study points out the potential of feral populations to reveal genes associated with specific disease resistance.     

Genetic control of streptococcus-induced hepatic granulomatous lesions in mice

Hepatic granulomatous lesions were induced in mice by a single intraperitoneal injection of 3 mg of disrupted Streptococcus pyogenes cell-wall material. Mice carrying the H-2 ^b or H-2 ^k haplotypes were highly susceptible to the induction and three weeks after the injection produced numerous granulomas. In contrast, mice of the H-2 ^d haplotype were resistant and produced only a few hepatic granulomas. Resistance was inherited as a dominant trait and in the backcross generation segregated together with the H-2 ^d phenotype. Testing of the H-2-recombinant mice indicated that the putative gene(s) determining resistance/susceptibility is located to the right of the S and to the left of the D region. Thes location corresponds to the recently described gene cluster consisting of tumor necrosis factor (TNF) and lymphotoxin genes and several BAT sequences. The known effect of TNF on granuloma formation in mice is consistent with a possible effect of TNF genes, and their variants, on S. pyogenes-inducibility of hepatic granulomas in mice. Address correspondence and offprint requests to: M. B. Zaleski.     

Genetic control of interleukin-2 production in inbred mice

BALB/c mice (H-2d haplotype) produced IL 2 better than C57BL/6 mice (H-2d haplotype). However genetic analysis in F2 generation demonstrated independent segregation of the IL 2 production intensity and H-2 haplotype. Investigation of the IL 2 production intensity in BALB/c, C57BL/6 and their F1 and F2 generation revealed that this was controlled by only one gene.     

Genetic control of T-Cell subset representation in inbred mice

Lyt-2+ T cells constitute a significantly greater proportion of the total peripheral T-cell population in C57BL mice than in BALB/c and other mouse strains. The inheritance of this differential representation of Lyt-2- vs. Lyt-2+ T cells was studied by two-color immunofluorescence analysis of peripheral T cell subsets in BALB/c, C57BL, F1 and F2 generations, and in CXB recombinant inbred strains. It was shown that the C57BL phenotype (low Lyt-2-/Lyt-2+ ratio) is a dominant Mendelian character. Studies of subpopulations of thymocytes and of early thymus emigrants indicate that the representation of mature Lyt-2- and Lyt-2+ T cells is influenced by mechanisms of selection or differential turnover in the peripheral lymphoid organs, but that thymic and prethymic influences may also play a role.     

Cage-change interval preference in mice

Before animal research facilities began using individually ventilated cage (IVC) systems for mice, cages were often changed one or more times per week. When using IVC systems, however, it is standard practice to change cages only once every 2-3 weeks. When deciding how often to change cages, personnel may consider the cost of labor needed to change the cage, as well as the cage type and bedding type, rather than animal preference or concern for animal well-being. The authors carried out a simple preference test in groups of mice. Mice were allowed to choose between an unsoiled cage and cages that had not been changed for 1 d, 7 d or 14 d. When evaluating where mice positioned their nests and the amount of time mice spent in the various cages, the authors found that the mice preferred the unsoiled cage. Younger mice (<150 d old) showed a stronger preference for the unsoiled cage than did older mice (>150 d old). Further studies are warranted to evaluate mice's preferences for cages changed at different intervals and to determine whether prolonging the interval between cage changes has any negative effects on mice.     

Genetics of food preference inDrosophila sechellia

To reveal the genetic mechanism of host selection in a monophagous fruit flyDrosophila sechellia, olfactory responses and oviposition preferences of this species were compared with those of closely related polyphagous species,D. simulans andD. melanogaster. Adult flies ofD. sechellia were strongly attracted to the ripe fruit ofMorinda citrifolia which is known to be the sole breeding site of this species. They were also attracted to the odor ofn-caproic acid which is contained in the ripe fruit ofM. citrifolia and is presumably responsible for the characteristic odor of the fruit. In contrast,D. simulans andD. melanogaster showed a strong repulsion ton-caproic acid. In parallel with the olfactory responses,D. sechellia females laid eggs preferentially on a medium containingn-caproic acid, to which the other two species showed an aversion. Genetic analyses using the hybrid progeny betweenD. sechellia andD. simulans suggested that the species differences in these behaviors are controlled by gene(s) located on the second chromosome.     

On food preference in the Red fox

• 1 Foxes treat different prey species in a variety of ways, eating, burying, or discarding them on the basis of preference.
• 2 Because foxes often utilize cached food and because they can remember which prey species is in a given cache the preference effect can be longstanding.
• 3 Evidence from the literature suggests that comparable effects of preference for different species of small mammals affects the diet of wild foxes and their behaviour in the same way as demonstrated in these experiments.
• 4 Certain distastes appear common to all foxes and most carnivores, for instance, insectivore and carnivore meat, in particular that of their own species.
• 5 An incidence of active cannibalism by a fox is reported.
• 6 The effect of food preference is shown to change during the course of one individual's life perhaps as a consequence of such factors as rearing cubs and competition for food.
• 7 One effect of the behavioural consequences of food preference is to defer the decision of what to eat.
• 8 That the fox will kill animals that it does not eat means that populations of animals that are not strictly fox prey are still at risk from fox predatory activity.

     

Genetic control of susceptibility to experimental allergic encephalomyelitis in mice

The genetic control of susceptibility to experimental allergic encephalomyelitis (EAE) was studied in mice. The results indicate that sensitivity to disease is not inherited in a simple Mendelian dominant way. Susceptibility to EAE is governed by genes located outside of the major histocompatibility complex and not byH-2-linkedIr genes. No correlation was observed between susceptibility to disease and the cellular immune response toward the small encephalitogenic protein.