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T R King

Publications and source records attributed to T R King.

18 recordsLinked to original sources
PubMed1992

Genetic and molecular analysis of recessive alleles at the pink-eyed dilution (p) locus of the mouse.

Recessive mutant alleles at the pink-eyed dilution (p) locus on mouse chromosome 7 reduce pigmentation of both the coat and eyes. Here we describe the properties and complementation interactions of 10 p alleles, including 6 not previously reported. Several alleles that cause additional phenotypes affecting development, reproduction, and behavior were shown to be deletions by using DNA probes derived from the p region. An alignment of functional and marker-defined units is proposed, giving a linear complementation map that orders at least four functional loci. The characterization of a nested set of deletions around p will facilitate detailed molecular analyses of the genes and developmental functions associated with this part of the mouse genome.

Alleles↗
PubMed1992

Telomere-related markers for the pseudoautosomal region of the mouse genome.

The pseudoautosomal (PA) region of the mammalian genome is the region of the X and Y chromosomes that shares extensive DNA sequence homology and is of special interest because it may play an essential role during male meiosis. We have identified three telomere-related restriction fragments from the PA region of the mouse genome, using an oligonucleotide probe composed of the mammalian telomere consensus sequence TTAGGG. PA assignment of two C57BL/6J-derived fragments was initially suggested by analysis of DNAs from progeny sired by C57BL/6J males carrying the rearranged Y chromosome, Y*: the hybridization intensity of both fragments was concordant with the sex-chromosome complement of the offspring. Further analysis indicated that both fragments were present in female and male F1, mice regardless of the sex of their C57BL/6J parent--a criterion for autosomal or PA linkage. Both fragments were closely linked to each other and located on the X chromosome distal to amelogenin (Amg)--in agreement with X or PA linkage. Confirmation of the PA derivation of these fragments was accomplished by following their segregation in a cross involving XY* males mated to DBA/2J females. A similar experiment identified a third PA-derived restriction fragment of LT/SvEi origin. Identification of PA-derived telomere-related restriction fragments will enable further genetic analysis of this region of the mouse genome.

Animals↗
PubMed1991

Meiotic mapping of murine chromosome 17: the string of loci around l(17)-2Pas.

We describe a genetic analysis of l(17)-2Pas, an embryonic lethal mutation on murine chromosome 17. Males transmitted the l(17)-2 allele to only 38% of their offspring, whereas females transmitted this allele at 50%. Two-point crosses revealed tight linkage between l(17)-2 and brachyury (T), and deletion mapping placed l(17)-2 outside of the hairpin-tail deletion (Thp). To map this mutation more precisely, we intercrossed hybrid mice that carry distinct alleles at many classical and DNA loci on chromosome 17 and obtained 172 animals recombinant in the T to H-2 region. Strong positive interference was observed over the 14 cM interval from T to H-2K. Thus, a single recombinant can be informative; one such recombinant places l(17)-2 distal of the molecular marker D17Leh66D. Robust genetic maps can be constructed with multilocus crosses that share anchor loci. DNA markers can be interpolated onto these maps retrospectively.

Animals↗
PubMed1991

Pleiotropic action of the murine quaking locus: structure of the qkv allele.

The spontaneous allele quakingviable (qkv) exerts effects on myelination and spermiogenesis. The defects generated by qkv were not separated in a multilocus mapping cross that provided a mapping resolution of 0.1 centiMorgans (cM). Furthermore, no distortions suggestive of a large chromosomal anomaly associated with qkv were apparent. One plausible interpretation is that the quaking locus contains more than one functional domain, either organized into overlapping genes or expressed by alternative splicing mechanisms. The cloning needed to analyze this locus will be enhanced by the very high resolution of the meiotic mapping cross reported here. The recombinational distances on this qkv map were compressed compared with those previously reported in a high-resolution map for qkl-1, an embryonic lethal allele of quaking induced by ethylnitrosourea. Additional crosses confirmed prior reports that the sex and the genetic background of the heterozygous parent can affect recombinational distances. These joint effects on recombination are strong enough to account for the discrepancy between the two maps. This variability of two-factor map values leads to the preferred multilocus map-building protocol discussed in the accompanying paper.

Animals↗
PubMed1991

Mapping anti-müllerian hormone (Amh) and related sequences in the mouse: identification of a new region of homology between MMU10 and HSA19p.

A panel of 78 backcross progeny, BALB/cJ x (BALB/cJ x CAST/Ei)F1, was used to map the gene encoding anti-Müllerian hormone (Amh), also called Müllerian inhibiting substance, to mouse Chromosome 10 (MMU10). This analysis identified a new region of linkage homology between human Chromosome 19p (HSA 19p) and MMU10 and localized an apparent recombinational hot spot in (C57BL/6J x Mus spretus)F1 females [compared with (BALB/cJ x CAST/Ei)F1 males] to the interval between phenylalanine hydroxylase (Pah) and mast cell growth factor (Mgf). In addition, eight unlinked polymorphic sequences, provisionally designated Amh-related sequences (Amh-rs1 through Amh-rs8), were identified by Southern blot analysis using Amh probes. Amh-rs1, -rs2, -rs4, and -rs7 were mapped to MMU1, 13, 12, and 15, respectively, by recombinant inbred (RI) strain and intraspecific backcross analyses. The NXSM RI strain distribution patterns for the four unmapped loci are also presented.

Animals↗
PubMed1991

Partial complementation by murine t haplotypes: deficit of males among t6/tw5 double heterozygotes and correlation with transmission-ratio distortion.

To evaluate whether sex reversal contributes to sex-ratio imbalance among t6/tw5 double heterozygotes, the cross performed by K. B. Bechtol (Genetical Research 39, 1982, 79-84), T/t6 x T/tw5, was repeated. Significantly more normal-tailed (t6/tw5) females than males were recovered. By contrast, sex ratios were normal among tailless progeny resulting from this cross and among all classes produced by control crosses. Hybridization of a Y-specific DNA probe with genomic DNA from phenotypic females revealed no XY, sex-reversed males. On the genetic backgrounds that generated only moderate transmission distortion of tw5 (81-85%), the overall viability of the doubly heterozygous progeny was only 50% and the sex-ratio skew among this class was strong. However, on a genetic background that displayed extreme tw5 transmission (99%), embryonic viability was more than 80% and the sex-ratio imbalance was weak.

Animals↗
PubMed1991

The mouse Y* chromosome involves a complex rearrangement, including interstitial positioning of the pseudoautosomal region.

Cytological analysis of the mouse Y* chromosome revealed a complex rearrangement involving acquisition of a functional centromere and centromeric heterochromatin and attachment of this chromosomal segment to the distal end of a normal Y* chromosome. This rearrangement positioned the Y* short-arm region at the distal end of the Y* chromosome and the pseudoautosomal region interstitially, just distal to the newly acquired centromere. In addition, the majority of the pseudoautosomal region was inverted. Recombination between the X and the Y* chromosomes generates two new sex chromosomes: (1) a large chromosome comprised of the X chromosome attached at its distal end to all of the Y* chromosome but missing the centromeric region (XY*) and (2) a small chromosome containing the centromeric portion of the Y* chromosome attached to G-band-negative material from the X chromosome (YX). Mice that inherit the XY* chromosome develop as sterile males, whereas mice that inherit the Y*X chromosome develop as fertile females. Recovery of equal numbers of recombinant and nonrecombinant offspring from XY* males supports the hypothesis that recombination between the mammalian X and Y chromosomes is necessary for primary spermatocytes to successfully complete spermatogenesis and form functional sperm.

Animals↗
PubMed1990

Cloning of the T gene required in mesoderm formation in the mouse.

The murine developmental mutation T identifies an essential gene in mesoderm formation. Embryos lacking normal gene activity fail to form the notochord, the entire posterior region and the allantois, and die at about 10 days of gestation. We have isolated the T gene using a combination of molecular and genetic techniques, thus making molecular tools available to study processes underlying mesoderm formation in the mouse.

Alleles↗
PubMed1989

Mapping to molecular resolution in the T to H-2 region of the mouse genome with a nested set of meiotic recombinants.

We describe a meiotic fine-structure mapping strategy for achieving molecular access to developmental mutations in the mouse. The induction of lethal point mutations with the potent germ-line mutagen N-ethyl-N-nitrosourea has been reported. One lethal mutation of prime interest is an allele at the quaking locus on chromosome 17. To map this mutation, quaking(lethal-1), we have intercrossed hybrid mice that carry distinct alleles at many classical and DNA marker loci on proximal chromosome 17. From this cross we have obtained 337 animals recombinant in the T to H-2 region. This number of crossovers provides a mapping resolution in the size range of single mammalian genes if recombinational hot spots are absent. DNA samples obtained from these recombinant animals can be used retrospectively to map any restriction fragment length polymorphism in the region. This set of DNA samples has been used to map the molecular marker D17RP17 just distal of quaking(lethal-1). With the nested set of crossover DNA samples and appropriate cloning techniques, this tightly linked marker can be used to clone the quaking locus.

Animals↗
PubMed1989

Electrocardiographic diagnosis of remote posterior wall myocardial infarction using unipolar posterior lead V9.

The accuracy of four electrocardiographic criteria for diagnosing remote posterior myocardial infarction was assessed prospectively in 369 patients undergoing exercise treadmill testing with thallium scintigraphy. Criteria included the following: 1) R-wave width greater than or equal to 0.04 s and R-wave greater than or equal to S-wave in V1; 2) R-wave greater than or equal to S-wave in V2; 3) T-wave voltage in V2 minus V6 greater than or equal to 0.38 mV (T-wave index); 4) Q-wave greater than or equal to 0.04 s in left paraspinal lead V9. Twenty-seven patients (7.3 percent) met thallium criteria for posterior myocardial infarction, defined as a persistent perfusion defect in the posterobase of the left ventricle. Sensitivities for the four criteria ranged from 4 to 56 percent, and specificities ranged from 64 to 99 percent. Posterior paraspinal lead V9 provided the best overall predictive accuracy (94 percent), positive predictive value (58 percent), and ability to differentiate patients with and without posterior myocardial infarction of any single criterion (p less than .0001). Combining the T-wave index with lead V9 further enhanced the diagnostic yield: the sensitivity for detecting posterior infarction by at least one of these criteria was 78 percent, and when both criteria were positive, specificity was 98.5 percent. It is concluded that a single, unipolar posterior lead in the V9 position is superior to standard 12-lead electrocardiographic criteria in diagnosing remote posterior myocardial infarction, and that combining V9 with the T-wave index maximizes the diagnostic yield.

Electrocardiography↗
PubMed1988

Saturation germ line mutagenesis of the murine t region including a lethal allele at the quaking locus.

The proximal region of mouse chromosome 17 contains many genes affecting embryonic development, germ cell differentiation, and the immune system. Although the study of natural variation, including t haplotypes, has yielded some information about the function of these genes, spontaneous variants often exhibit manifold genetic effects and are generally not carried on inbred backgrounds. To clearly connect phenotypes with the actions of individual genes, mutants in which genes are altered singly are needed. Therefore, we used a highly efficient point mutagen, N-ethyl-N-nitrosourea, in combination with classical breeding schemes to induce and identify recessive lethal mutations in the t region. Of 350 mutagenized gametes examined, at least 10 independent recessive embryonic lethal mutations have been identified; an additional two are perinatal lethals. A spontaneous brachyury mutation, TWis, arose on a genetic background that permits high-resolution mapping of the induced recessive mutations against cloned DNA sequences from the t region. One lethal mutation is an allele at the quaking locus. The multiple alleles of quaking and the feasibility of high-resolution mapping permit investigation of the pleiotropic action of this locus in mammalian development.

Alleles↗
PubMed1987

Neuroendocrine and behavioral effects of intrathecal capsaicin in adult female rats.

Neural feedback from the gonads and the reproductive tract has an integral role in normal reproductive function in female rats. To further assess the role of sensory feedback in neuroendocrine control, the effects of an intrathecal injection of the neurotoxin, capsaicin (100-125 micrograms) into the lumbosacral region of the spinal cord on reproductive function was tested in female rats. In addition, the effects of capsaicin on the response to noxious heat and pressure were tested. Intrathecal capsaicin had no effect on estrous cycles, ovarian compensatory hypertrophy or female sexual behavior. However, capsaicin treated animals showed a dramatic reduction in fertility, relative to vehicle treated control rats and this was shown to be due to the reduced capacity of vaginal/cervical stimulation to produce pseudopregnancy. Consistent with a selective loss in the effectiveness of cervical stimulation, immobilization produced by vaginal probing was reduced in capsaicin treated rats, but this response slowly recovered across time in some animals. Similarly, the ability of vaginal probing to induce a lordotic response during estrogen treatment was reduced in the capsaicin treated animals. The capsaicin treated animals showed analgesia to noxious heat, as measured by the tail flick test, but showed a normal foot withdrawal in response to pressure. The analgesic effect of vaginal stimulation on noxious pressure was unaltered in the capsaicin treated rats. Finally, the neurotoxic effect of capsaicin was verified in terms of a quantitative reduction in substance P immunoreactivity in the dorsal horns of the lumbosacral region of the spinal cord of capsaicin treated rats, relative to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Hypersensitivity reaction to desipramine.

Adverse reactions to the tricyclic antidepressant drugs imipramine and desipramine have been described and include eosinophilia, pulmonary infiltrates with eosinophilia, and elevated total serum IgE levels. The immunologic mechanism accounting for these adverse reactions has not been elucidated. This article describes a patient manifesting bronchospasm, profound eosinophilia, and elevated serum IgE levels after therapy with desipramine that resolved rapidly after withdrawal of the drug. Immunologic investigations failed to demonstrate specific IgE directed against a protein conjugate of desipramine but demonstrated the ability of desipramine to induce mast cell degranulation with direct intradermal skin challenges.

Desipramine↗
PubMed1986

Neuroestrogenic control of feeding behavior and body weight in rats with kainic acid lesions of the lateral septal area.

The role of the lateral septal area (LS) in the regulation of energy balance and the estrogenic control of feeding behavior in the female rat has been examined. Food intake (FI) and body weight (BWt) were measured daily following kainic acid (KA) LS lesions (KALS) to assess any regulatory changes in energy balance. In all animals KA lesions of the LS produced major cell loss in the LS; however the extent of damage was variable. Associated with KA lesions of the LS was the concurrent loss of CA3-CA4 cell groups in the hippocampus which was comparable for all the lesioned animals. The extent of septal damage was quantified morphometrically and correlated with changes in FI and BWt following estrogen treatment. The significant effects of the KALS lesions, relative to the control animals were: an increase in BWt which was statistically significant 22 days following brain surgery, an increase in daily FI which was significant by day 6 post surgery, an attenuation in the anorexic effects of estrogen on FI and BWt, and a significant decrease in the present days of vaginal estrus. Moreover, the anorexic effects of estrogen were significantly correlated with the extent of LS damage, but not the amount of hippocampal damage. The present study confirms that an increase in BWt is produced by KA lesions of the LS and further indicates that a sustained period of increased FI precedes the increase in BWt.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Differential effects of neurotoxic lesions on psychoneuroendocrine functions.

The use of neurotoxic agents has provided new insight into the functions of the septal region. The psychoneuroendocrine effects of kainic acid (KA) lesions in the lateral septum (LS) have been confirmed, and we have compared the effects of these lesions to those following lesions of the medial septum (MS) and hippocampus (HP). In addition, the effects of the cytotoxin ibotenic acid (Ibo), have been studied. The alterations in psychoneuroendocrine functions resulting from the cytotoxic lesions have been compared to those from electrolytic septal lesions (DCLS) and sham operations. KA and Ibo lesions of the LS resulted in extensive bilateral loss of neurons in the LS; however, KALS lesions also resulted in cell loss in the CA3-CA4 cell regions of the HP. In contrast, KA and Ibo lesions of the MS did not produce any obvious cell loss in the MS. KA lesions of the HP produced extensive CA3-CA4 cell loss and a reduction in the size of the fornix and rostral septum. The behavioral and endocrine effects of these lesions were, relative to controls: the KALS group exhibited fewer percent days of vaginal estrus, increased ovarian compensatory hypertrophy (OCH), increased body weight (BWt), attenuation in the anorexic effects of estrogen, and decreased female sexual behavior. The KAMS group exhibited a transitory increase in BWt and increased male sexual behavior. IboLS group demonstrated a greater percent days of vaginal estrus and increased female sexual behavior whereas the IboMS group exhibited a decrease in OCH. The KAHP group exhibited a partial attenuation in the anorexic effects of estrogen on food intake and BWt gain. The DCLS group demonstrated increased female sexual behavior. These results indicate that the septal region is involved in both facilitatory and inhibitory modulation of a variety of estrogen responsive processes and further suggest that the MS and LS have different psychoneuroendocrine functions.

Animals↗
PubMed1985

The effects of unilateral frontolateral hypothalamic knife cuts and asymmetrical unilateral septal lesions on lordosis behavior of rats.

It has been shown that the medial hypothalamus exerts facilitatory control over female sexual behavior in the rat whereas the septal area exerts inhibitory control over lordosis behavior. The present study assessed whether the septal area exerts its inhibitory control over lordosis behavior via efferent connections with the mediobasal hypothalamus. Anatomical studies using retrograde tracers verified that cell bodies located in the lateral septal area project ipsilaterally to the mediobasal hypothalamus. Based upon the predominantly ipsilateral connection between the lateral septum and mediobasal hypothalamus, unilateral frontolateral knife cuts were produced on the left or right side of the mediobasal hypothalamus or else sham surgeries. Subsequently all animals were given unilateral electrolytic septal lesions on the right side of the brain. These animals had septal damage that was located either ipsilateral or contralateral with respect to the knife cuts. Female sexual behavior was tested following the hypothalamic knife cuts and retested after unilateral septal lesions. Unilateral hypothalamic knife cuts on either side of the brain had no detectable effect on female sexual behavior when compared to the sham group. However, following unilateral septal lesions a significant increase in lordosis behavior was observed in all groups following treatment with estrogen alone. There were no differences in lordosis behavior between the groups which had septal lesions located ipsilateral vs. contralateral with respect to the hypothalamic knife cuts. These results support the hypothesis that the facilitation in lordosis behavior associated with electrolytic septal lesions is not mediated by neural connections between the septal area and mediobasal hypothalamus. These two brain areas thus appear to exert separate and independent control over female sexual behavior.

Animals↗