Induction of a ragweed-specific allergic state in Ir-gene-restricted nonresponder mice.

Mice of the inbred strains, C57BL/6 and C57BL/10 (H-2b), are genetically incapable of developing IgE antibody responses to ragweed pollen extract (RE) or its dinitrophenylated derivative, DNP-RE. This nonresponsiveness has previously been thought to reflect the absence of a relevant H-2-linked Ir genes controlling responses of inbred mice to these antigens. However, pretreatment of H-2b mice with either low doses of ionizing X irradiation or cyclophosphamide abrogates the nonresponder status of such animals, apparently by removal of a suppressive mechanism normally inhibiting development of IgE responses to these antigens. The implications of these findings for mechanisms of genetic control of IgE antibody synthesis and the Ir-gene concept are discussed.

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H-2 mutation affecting immune response to Thy-1.1 antigen

Journal of Experimental Medicine ◽

10.1084/jem.145.6.1602 ◽

1977 ◽

Vol 145 (6) ◽

pp. 1602-1606 ◽

Cited By ~ 13

Author(s):

M Zaleski ◽

J Klein

Keyword(s):

Immune Response ◽

Inbred Mice ◽

Serum Antibody ◽

Inbred Strains ◽

Antibody Responses ◽

Chromosome 9 ◽

Chromosome 17 ◽

Target Cells ◽

Histocompatibility Complex ◽

The Right

Mouse thymus, thymus-derived lymphocytes, and brain share an antigen determined by gene at the Thy-1 locus in chromosome 9 (1). Two alleles have been identified at this locus: Thy-1(a), coding for antigen Thy-1.1 (or θ-AKR) present in AKR and seven other strains; and Thy-1(b), coding for antigen Thy-1.2 (or{teta}-C3H) and present in C3H and all the remaining inbred strains. Injection of AKR thymocytes into inbred mice carrying the Thy-1(b) allele results in an immune response that can be measured either serologically by determining the level of antibodies in the recipients serum (1) or by counting plaque- forming cells (PFC) detectable in spleens of the recipients by means of an assay, with AKR thymocytes as target cells(2). The magnitude of PFC and serum antibody responses after a single thymocyte injection depends on the genetic make-up of the recipient. Three genes controlling the PFC response to the Thy- 1.1 antigen have been identified: Ir-Thy-1A and Ir-Thy-1B, which are closely linked to the major histocompatibility complex (H-2) of the mouse (3-6), and Ir-5, which is located at a distance of 17 cm to the right of the H-2 complex on chromosome 17 (6). Previous genetic mapping with H-2 recombinant strains has indicated that the two Ir-Thy-1 loci are located to the left of the IC subregion (7). Further experiments strongly suggested that either one or both Ir-Thy-1 loci map to the K rather than the I region of the H-2 complex (8). In this report, the study of an H- 2 mutant, CBA-H-2(ka) (M523) (9), and its parental strain, CBA/LacStoY (CBA) provided further evidence that one of these loci apparently resides in the K region and might even be identical with the H-2K locus in that region.

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THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY

Journal of Experimental Medicine ◽

10.1084/jem.119.1.21 ◽

1964 ◽

Vol 119 (1) ◽

pp. 21-39 ◽

Cited By ~ 83

Author(s):

Sven-Eric Svehag ◽

Benjamin Mandel

Keyword(s):

Antibody Formation ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Whole Body ◽

High Dose ◽

Antibody Synthesis ◽

Antigen Dose ◽

X Irradiation ◽

Virus C ◽

Kinetics Of

Transient 19S antibody formation was induced in rabbits by single or repeated stimuli with a small dose of poliovirus. Available evidence indicated that cessation of 19S synthesis was due to lack of continuous antigenic stimulation and not to loss of cells participating in antibody formation. "Immunological memory" in 19S antibody formation was demonstrable only within 2 to 3 days following discontinuation of synthesis but not thereafter. Following stimulation with a high dose of polio-virus both 19S and 7S antibodies were formed. The kinetics of their formation differed in several respects: (a) 19S antibody preceded 7S antibody by ⩾1½ days; (b) 19S antibody rose to peak titers at a rapid exponential rate within 1 week, while 7S antibody increased at a slow decelerating rate for ⩽3 weeks; (c) 19S antibody formation was short-lasting while 7S antibody synthesis endured. A renewed formation of both antibodies occurred following restimulation with a high antigen dose. The secondary 19S and 7S antibody responses were similar to the respective primary responses, and the preexistence of 7S antibody synthesis did not detectably alter the secondary 19S response. Both 19S and 7S antibodies were formed and the kinetics of their formation was similar (a) for infectious and non-infectious (UV-) poliovirus antigen; (b) for the serologically unrelated poliovirus and Coxsackie B-4 virus; (c) when poliovirus was administered by different routes; (d) when 1-day-old or adult rabbits were immunized; (e) in antibody responses to poliovirus in rabbit, guinea pig, and man. Whole body x-irradiation 20 hours prior to antigenic stimulus (high dose) resulted in delayed but markedly prolonged 19S antibody formation and inhibition of 7S antibody synthesis. Thus, the formation of 19S and 7S antibody differed in (a) antigen dose requirements for induction and maintained synthesis; (b) kinetics; (c) retention of memory; and (d) sensitivity to prior x-irradiation. These differences are best explained on the assumption that the two antibodies are produced by different cells.

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Inherited histocompatibility changes in progeny of irradiated and unirradiated inbred mice

Genetics Research ◽

10.1017/s0016672300004225 ◽

1965 ◽

Vol 6 (3) ◽

pp. 330-340 ◽

Cited By ~ 91

Author(s):

D. W. Bailey ◽

H. I. Kohn

Keyword(s):

Mutation Rate ◽

Inbred Mice ◽

Spontaneous Mutation ◽

Inbred Strains ◽

Mutant Mice ◽

Antigen Specificity ◽

Spontaneous Mutation Rate ◽

Doubling Dose ◽

X Irradiation ◽

Hybrid Mice

(1) F1-hybrid mice derived from a cross of the highly inbred strains: C57BL/6 and BALB/c, were tested for inherited changes of histocompatibility by an orthotopic inter-exchange of tail-skin grafts. The fathers of tested mice received either 522 rads of gonadal X-irradiation, or received no irradiation 2 months prior to mating.(2) Thirty-two mice with altered histocompatibilities were found in a total of 2572 complete tests. All of those mutant mice (twenty-one) that produced an adequate number of offspring were shown to pass the incompatibility on to their progeny.(3) Mutants were classified as to whether they effected a gain, a loss or both a gain and a loss in antigen specificity as determined by whether they rejected skin of donor mice or their skin was rejected by host mice. Twenty-six were clearly of the gain type, five were most likely gain type and only one showed both a loss and a gain effect. There was no clearcut evidence that loss types had occurred. The preponderance of gain types was tentatively explained as an artifact of the system used for the assay.(4) Several of the detected mutants were probably from parents carrying mutations that originated in past generations, for some mutant mice occurred in clusters.(5) There was no apparent effect of paternal irradiation (522 rads) on mutation frequency. The induced mutation rate was estimated to be less than 2·6 × 10−5/ gamete/rad.(6) Independent data on isografts from F1 hybrids of proven non-carrier pedigreed parents provided an estimate of spontaneous mutation rate of 6·75 × 10−3/ gamete.(7) The estimate of doubling dose (greater than 260 rads) was consistent with the estimates for recessive lethals and visibles in mice.

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Suppression of IgE antibody responses by NKT cells—mechanisms of NKT cell-mediated regulatory function

International Congress Series ◽

10.1016/j.ics.2005.08.002 ◽

2005 ◽

Vol 1285 ◽

pp. 179-183

Author(s):

Satoshi Kojo ◽

Michishige Harada ◽

Ken-ichiro Seino ◽

Masaru Taniguchi

Keyword(s):

Nkt Cells ◽

Antibody Responses ◽

Regulatory Function ◽

Nkt Cell ◽

Ige Antibody

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Genetic modulation of initial sensitivity to Δ9-tetrahydrocannabinol (THC) among the BXD family of mice

10.1101/2021.01.08.425948 ◽

2021 ◽

Author(s):

Cory Parks ◽

Chris M Rogers ◽

J. Pjotr Prins ◽

Robert W. Williams ◽

Hao Chen ◽

...

Keyword(s):

Single Dose ◽

Drugs Of Abuse ◽

Cannabinoid Receptor ◽

Inbred Mice ◽

Strain Differences ◽

Inbred Strains ◽

Thermal Stimulus ◽

Motor Impairments ◽

Initial Sensitivity ◽

Acute Responses

Cannabinoid receptor 1 activation by the major psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), produces motor impairments, hypothermia, and analgesia upon acute exposure. In previous work, we demonstrated significant sex and strain differences in acute responses to THC following administration of a single dose (10 mg/kg, i.p.) in C57BL/6J (B6) and DBA/2J (D2) inbred mice. To determine the extent to which these differences are heritable, we quantified acute responses to a single dose of THC (10 mg/kg, i.p.) in males and females from 20 members of the BXD family of inbred strains derived by crossing and inbreeding B6 and D2 mice. Acute THC responses (initial sensitivity) were quantified as changes from baseline for: 1. spontaneous activity in the open field (mobility), 2. body temperature (hypothermia), and 3. tail withdrawal latency to a thermal stimulus (analgesia/antinociception). Initial sensitivity to the immobilizing, hypothermic, and antinociceptive effects of THC varied substantially across the BXD family. Heritability was highest for mobility and hypothermia traits, indicating that segregating genetic variants modulate initial sensitivity to THC. We identified genomic loci and candidate genes, including Ndufs2, Scp2, Rps6kb1 or P70S6K, Pde4d, and Pten, that may control variation in THC initial sensitivity. We also detected strong correlations between initial responses to THC and legacy phenotypes related to intake or response to other drugs of abuse (cocaine, ethanol, and morphine). Our study demonstrates the feasibility of mapping genes and variants modulating THC responses in the BXDs to systematically define biological processes and liabilities associated with drug use and abuse.

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Examining basal chloride transport using the nasal potential difference response in a murine model

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.281.5.l1173 ◽

2001 ◽

Vol 281 (5) ◽

pp. L1173-L1179 ◽

Cited By ~ 11

Author(s):

Kristine G. Brady ◽

Thomas J. Kelley ◽

Mitchell L. Drumm

Keyword(s):

Cystic Fibrosis ◽

Chloride Transport ◽

Inbred Mice ◽

Inbred Strains ◽

Potential Difference ◽

Transmembrane Conductance Regulator ◽

Transmembrane Conductance ◽

Inbred Strains Of Mice ◽

Cystic Fibrosis Transmembrane

Epithelia of humans and mice with cystic fibrosis are unable to secrete chloride in response to a chloride gradient or to cAMP-elevating agents. Bioelectrical properties measured using the nasal transepithelial potential difference (TEPD) assay are believed to reflect these cystic fibrosis transmembrane conductance regulator (CFTR)-dependent chloride transport defects. Although the response to forskolin is CFTR mediated, the mechanisms responsible for the response to a chloride gradient are unknown. TEPD measurements performed on inbred mice were used to compare the responses to low chloride and forskolin in vivo. Both responses show little correlation between or within inbred strains of mice, suggesting they are mediated through partially distinct mechanisms. In addition, these responses were assayed in the presence of several chloride channel inhibitors, including DIDS, diphenylamine-2-carboxylate, glibenclamide, and 5-nitro-2-(3-phenylpropylamino)-benzoic acid, and a protein kinase A inhibitor, the Rp diastereomer of adenosine 3′,5′-cyclic monophosphothioate ( Rp-cAMPS). The responses to low chloride and forskolin demonstrate significantly different pharmacological profiles to both DIDS and Rp-cAMPS, indicating that channels in addition to CFTR contribute to the low chloride response.

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