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At least 19 recordsLinked to original sources
PubMed1990

Neuropeptide content in pancreas and pituitary of obese and diabetes mutant mice: strain and sex differences.

The nature of the primary genetic defects in ob/ob and db/db mice are unknown. Both the obese (ob) and diabetes (db) mutations produce similar, multicomponent obese-hyperinsulinemic syndromes when maintained in the same strain of mouse. In an attempt to find differences between these mutations in neuroendocrine function affecting the islets of Langerhans or the pituitary, tissue content of four neuropeptides that are known to be capable of influencing the rate of insulin secretion was examined in obese (ob/ob) and diabetes (db/db) mice. In the first study, C57BL/6Job/ob and control males were studied at 3, 4, and 11 weeks of age. In the second study, db/db mice of both sexes and two inbred strains (C57BL/6J and C57BL/KsJ), which differ markedly in the severity of expression of the diabetes phenotype, were studied at 3 weeks of age, before the development of hyperglycemia and secondary consequences thereof. Immunoreactive peptides were measured in acetic acid extracts of pancreas and pituitary. No differences between male ob/ob and db/db mice of the C57BL/6J strain were found. Marked sex differences in lean control mice were found at 3 weeks of age in pancreatic Met-enkephalin-LI and galanin-LI (with two- to threefold higher content in males). Low pancreatic content (50% to 70% lower than in control mice) of galanin-LI, Met-enkephalin-LI and Leu-enkephalin-LI was associated with hyperinsulinemia in male B6 ob/ob and db/db mice at 3 weeks of age, though not in B6 db/db females and not in BKs db/db mice of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Xenotropic virus-related restriction patterns of non-H-2 histocompatibility mutant mice strains.

The relationship between alteration in the number of xenotropic virus-related sequences and non-H-2 histocompatibility (H) mutations in mice was investigated. Mutant classifications included gain, loss, and loss-gain mutations. Genomic DNA from a panel of non-H-2 H mutant strains on the C57BL/6 and BALB/c backgrounds was digested with a set of restriction enzymes with varying numbers of sites within endogenous xenotropic-related sequences. The digested DNA was then resolved on agarose gels. Southern blots of digested DNA were hybridized with the pXenv probe specific for the env sequence of xenotropic viral sequences. The number of hybridizing bands varied from 7 to 19, depending on the restriction enzyme and inbred background. Most mutant strains were identical in their restriction patterns to the respective background strains. However, two B6 mutant strains, KH84 and HZ54, differed from C57BL/6 at a single band which appeared to be inherited from BALB/c in the derivation of the two congenic strains. The HZ43 strain lacked a male-specific band shared by both C57BL/6 and BALB/c; this loss was evidently independent of the original mutation which was observed to be autosomal. However, the KH148B and KH84 strains on the C57BL/6 background lacked single B6 bands. Both mutants were classified as gain mutants. An examination of previous reciprocal graft rejection patterns and retrovirus linkage to non-H-2 H loci indicated a strong inverse relationship between a linked retroviral sequence and presentation of a non-H-2 H antigen. This inverse correlation is consistent with reports of gene inactivation following retroviral insertion.

Animals↗
PubMed1982

[Anomalous relationships between oocyte growth and the proliferative activity of the follicular epithelium in the ovaries of LT/Sv strain mutant mice].

A comparison of the number of follicular epithelium cells and its proliferative activity with the oocyte diameter upon normal (ICR mice) and abnormal (LT/Sv mice) oogenesis was carried out. Two populations of monolayered follicles were found in the LT/Sv mice. The population of normal follicles providing for reproductive function is characterized by a distinct correlation between the follicle size, number of DNA-synthesizing follicular cells and oocyte diameter. The group of abnormal follicles contains large oocytes the growth of which is ahead of the development of granulosa cells. The number of DNA-synthesizing cells of monolayered follicular epithelium is 6 times less than in the normal follicles. 96% of parthenogenetically cleaving eggs were found in such abnormal monolayered follicles as well, the number of DNA-synthesizing cells being 14 to 17 times less than that in the normal follicles. Possible mechanism of this phenomenon are discussed.

Animals↗
PubMed1996

Dopamine requires the unoccupied progesterone receptor to induce sexual behavior in mice.

Using the recently generated mutant mice strain (PRKO) carrying a null mutation for the progesterone receptor (PR) gene by gene targeting, we examined the critical role of PR as a coordinator of key regulatory events involved in the steroid hormone and dopamine-facilitated sexual behavior in female mice. In vitro one-point binding analyses of estradiol benzoate (EB)-induced cellular PRs and immunohistochemistry of PR in the mediobasal hypothalamus demonstrated a reduction in binding in the homozygous females, equivalent to background levels seen in EB-unresponsive tissue. The biochemical findings correlated well with the behavioral observations, with the wild type females exhibiting high levels of lordosis, while the homozygous females showed minimal lordosis in response to mating by male mice. As a critical validation of our earlier studies on ligand-independent activation of PRs by dopamine, we examined the facilitation of sexual behavior by a dopamine agonist in the null mutants. Wild type females having the full complement of PRs exhibited high levels of lordosis, while the homozygous females showed minimal lordosis in response to dopamine. To determine whether this reduced response was due to a general lack of ability to express lordosis, mice were treated with another neurotransmitter, serotonin. No significant difference in the serotonin-facilitated lordosis response was observed between the wild type and the homozygous females. We conclude that multiple signal transduction pathways coexist in the neuroendocrine system for reproductive behavior, with PR acting as a transcriptional mediator for dopamine, as well as progesterone, to achieve integration of neural communication in the central nervous system.

Animals↗
PubMed1985

Genetic resistance to murine cryptococcosis: increased susceptibility in the CBA/N XID mutant strain of mice.

In a survey of 301 normocomplementemic inbred mice (belonging to nine different strains: BALB/cN nu/nu and nu/+, CBA/N, C57BL/KsJ, C57BR/cdJ, CBA/CaJ, BRVR, DW/+, and C57BL/6J) for natural resistance to Cryptococcus neoformans, cumulative survival values were found to range from 12 to 22 days. When the average organ weights of infected animals were compared with reference values obtained in uninfected mice of the same age and genetic lineage, the following changes were documented. In the CBA/N strain, the mean spleen and brain weights increased 313 and 13.5%, respectively, whereas the mean liver weight remained unchanged. In the CBA/Ca strain, cerebral cryptococcosis was the dominant clinical feature, and a 54% increase in mean brain weight was recorded at the time of death. The averaged liver weight was drastically lower, whereas spleen weight values evinced a biphasic pattern of transient splenomegaly followed by involution. At the median time of death, CBA/N mice had significantly more cryptococci in the liver and spleen than corresponding CBA/Ca mice. In the (CBA/N X CBA/Ca)F1 mice, susceptibility to C. neoformans segregated according to the sex-linked inheritance of the X-linked immunodeficiency (xid) gene. It is concluded that (i) susceptibility to cryptococcosis is under multigenic control, (ii) the xid locus on the X chromosome influences susceptibility to cryptococcosis, and (iii) xid mice behave differently than CBA/Ca mice in their organ response during the course of the infection.

Animals↗
PubMed1995

EMG analysis of harmaline-induced tremor in normal and three strains of mutant mice with Purkinje cell degeneration and the role of the inferior olive.

1. The effects of intraperitoneal injections of 10 mg/kg harmaline were tested in normal mice and three strains of cerebellar mutant mice with Purkinje cell degeneration. Ten normal (wild-type) mice (+/+), as well as five lurcher (lc/+), six nervous (nr/nr), and eight Purkinje cell degeneration (pcd/pcd) mutants were implanted with chronic electromyogram (EMG) electrodes in the hamstring and quadriceps muscle groups of the right hindlimb. 2. EMGs were recorded in each of the mice during spontaneous activity before and after intraperitoneal injections of 0.3 ml harmaline (10 mg/kg). Spectral analysis was used to quantify the amplitude and frequency of tremor found in the EMGs after harmaline administration. Normal mice responded to harmaline with strong, continuous 11- to 14-Hz tremor. Mutants from the pcd/pcd strain also reacted with continuous tremor, but of lower amplitude and frequency. In contrast, nr/nr mutants exhibited intermittent paroxysmal tremor lasting for only a few seconds, and lc/+ mutants showed no evidence of tremor whatsoever. 3. In order to detect covert tremor that was possibly not revealed by focal intramuscular EMG recordings, several mutant and normal mice were also tested on a suspended platform to which an accelerometer was attached. The results confirmed the findings from EMG recordings. 4. An incidental observation made during the course of this study was that harmaline tremor disappeared from the normal mouse during swimming and reappeared when the animal was withdrawn from the water. 5. Although Purkinje cells appeared to increase both the depth of modulation and the frequency of tremor, the inhibitory action of the cerebellar cortex does not seem to be essential for the generation of tremor. 6. Parasagittal cerebellar sections of the normal, wild-type mice and the three strains of cerebellar mutant mice of various ages were stained with cresyl violet and examined for Purkinje cell degeneration. Purkinje cell degeneration was found to be complete in the pcd/pcd and lc/+ strains. Although an initial examination of parasagittal sections of the nr/nr strain failed to find any surviving Purkinje cells, further examination of sections cut in the coronal plane revealed small clusters of Purkinje cells in the vermal area of the posterior lobe. 7. The retrograde transport of wheat-germ-agglutinin-conjugated horseradish peroxidase (WGA-HRP) pressure-injected into the cerebellar cortex was used to study the olivocerebellar projections in the wild-type mice and the three strains of cerebellar mutant mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Role of bone marrow cells in autoantibody production and lymphoproliferation in the novel mutant strain of mice, CBA/KlJms-lprcg/lprcg.

The novel mutant gene, lprcg, is allelic with lpr, but complements the gld gene in induction of lymphoproliferation. Mice with this autosomal recessive mutation, CBA/KlJms-lprcg/lprcg (CBA-lprcg), served in this study to analyze the abnormalities of bone marrow (BM) stem cells responsible for autoantibody production and lymphoproliferation by BM transfer experiments. Transferred CBA-lprcg BM cells might have differentiated into so-called double-negative, anomalous lymphoid cells and caused production of autoantibodies such as anti-DNA antibodies in the environment of normal CBA/KlJms-(+)/+ (CBA-(+)) mice. Macroscopic graft-vs.-host-like disease as reported in lpr----non-lpr BM transfer was not observed in these recipients. In this BM chimera, however, lymphoproliferation did not ensue and the host's lymph nodes became atrophic. The lymphoproliferation required the coexistence of lprcg BM cells and lprcg lymph nodes in CBA-(+) mice. The results indicate that the functions of the lprcg gene are expressed at both BM and lymph node levels. Thus, this mutant strain of mice should provide an excellent model for analyzing aberrant lymphocyte differentiation from the BM cells leading to autoimmunity and lymphoproliferative disorder.

Animals↗
PubMed2006

Comparison of embryonic cerebellar graft survival in adult Lurcher mutant mice of strains C3H and C57Bl/7.

Lurcher mutant mice suffer from complete loss of cerebellar Purkinje cells. The aim of the work was to compare the solid embryonic cerebellar graft survival in adult Lurcher mutant mice derived from strains C3H and C57Bl/7 and to assess the morphology of the grafts. Embryonic cerebellar tissue was obtained from 12-13 days mice embryos expressing green fluorescent protein (GFP). Embryonic cerebellum was injected with a glass microcapillary into the cerebellum of adult Lurcher mutant mouse. Host mice were sacrificed 2-12 weeks after the transplantation. Brainstems and cerebella were examined histologically. The graft and graft derived GFP-positive cells were detected according to their green fluorescence. To visualise the structure of the graft Nissl staining was used. Graft survival percentage was evaluated in groups of mice sacrificed during the first, second or third month after the transplantation. The graft was found in all C57Bl/7 mice and in 90.9% of C3H mice examined within one month after the transplantation. In the second month the graft was present in 83.3% of C57Bl/7 and 50.0% of C3H mice. Till the third month the graft survived in 68.2% of C57Bl/7 mice and 22.2% of C3H mice. In C57Bl/7 mice a cerebellar structure was developed in the graft and migration of graft derived-cells to the host tissue was observed more often than in C3H mice. C567Bl/7 mice seem to be more suitable for experiments testing functional consequences of transplantation into the cerebellum requiring good long-term graft survival.

Animals↗
PubMed1982

Comparative levels of endogenous myelin basic protein-serum factors (MBP-SFs) in adult and suckling mice (B6CBAF1 and B6C3HF1, strains) and in neurologically mutant mice of the same genetic background.

Normal adult B6C3HF1 and B6CBAF1 mice contained at least 10 times higher levels (1.17 microM) of endogenous myelin basic protein-serum factors (MBP-SFs) than previously found in adult Lewis rats. In rat MBP-SF levels in the adult (0.03 microM) were much less than in the suckling animals (0.74 microM). In mice, by contrast, the adult (1.17 microM) and suckling (0.75 microM) levels were similar. Suckling mice from 9 different neurologically mutant strains and their clinically normal littermates had MBP-SF levels (0.5 microM) slightly below that of normal suckling mice of the same genetic background (0.75 microM).

Animals↗
PubMed2003

[In vivo functional analysis of the neuropeptide PACAP using gene-targeted mice].

Mutant strains of mice with precise genetic mutations generated by gene-targeting technology have proved to be useful tools for linking specific genes with biological processes in vivo and serve as models for human diseases. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved neuropeptide that is widely expressed in the mammalian brain, and it has been implicated in a broad variety of physiological and pathophysiological processes. To assess the function of PACAP in vivo, recently, we have generated PAC1 receptor- and PACAP-targeted mice and transgenic mice overexpressing PACAP in the pancreatic beta-cells. The phenotypes of these mutant mice revealed both expected and unexpected roles of PACAP in the brain and pancreatic functions. A significant contribution of genetic background as well as environmental factors to the knockout phenotypes was also observed. In this article, we briefly describe the technique of gene targeting and discuss how this method was used to generate PACAP and its receptor deficient mice. We also analyze how these mutants can contribute to our understanding of the molecular mechanism underlying higher nervous functions.

Animals↗
PubMed1987

Cryopreservation of strains and mutant genes in mice.

Three kinds of freezing methods were tested with embryos of DNI strain. The survival rate after thawing was 47.5%, 66.7% and 77.8% in the 2-step method, modified slow freezing method and modified 2-step method, respectively. Then, the modified 2-step method was applied to the embryos from 7 strains and a pair of interstrain crosses. PMSG treatment at the beginning of diestrus following HCG treatment after 48 hrs resulted in much yield of 8-16-cell embryos in all strains. The average number for each strain was as follows: DNI; 18.9, DDN; 13.0, BS; 20.4, C57BL/6; 12.9, DBA/2; 17.5, CRN; 19.8, PAN; 13.7 and DNI x C57BL/6-Ay; 21.7. Development of frozen-thawed embryos in culture varied among strains. Proportion of embryos that developed to the morula or blastocyst stage was as follows: DNI; 64.6%, DDN; 71.9%, BS; 53.6%, C57BL/6; 57.3%, DBA/2; 65.0%, CRN; 52.5%, PAN; 17.4% and DNI x C57BL/6-Ay; 44.1%. These results indicate that the ability of embryos to survive freezing and thawing is influenced by their genetic background. Live young were produced from DNI, DDN, BS and DNI x C57BL/6-Ay embryos after transfer to recipients. Comparative assessment of the developmental ability of frozen-thawed embryos after transfer among strains should be performed in further study.

Animals↗
PubMed1990

Deterioration of hearing function in mice with neural crest defect.

Cochlear potentials were recorded in black-eyed white-mutant mice (strains W/Wv and S1/S1d) during the first months of postnatal life. In these animals melanocytes from the neural crest do not reach the stria vascularis. Hearing thresholds indicated by the compound action potential of the auditory nerve progressively increased. Hearing loss in comparison with the control CBA mice amounted 40 dB six weeks after birth, at eight months practically all mutants were deaf. Endocochlear potential was near zero already in the majority of 6 week-old animals. Abnormalities were observed also in intracellular potentials of the stria vascularis cells which were recorded in vitro and dye-marked. While in marginal cells of CBA mice positive potentials of about 10 mV were recorded, potentials of marginal cells in mutants were near zero. Basal cell potentials were negative in CBA mice (approximately -25 mV) and positive in young mutants (approximately +12 mV). However, in mutants older than 3 months the intracellular potentials of basal cells changed to negativity (approximately -10 mV). The results demonstrate gradual deterioration of hearing function observed in both W/Wv and S1/S1d mutants during first months of the postnatal life. In addition to the dysfunction of stria vascularis, where intermediate cells are missing, also the function of receptors progressively deteriorates.

Action Potentials↗
PubMed1986

Performance of normal and neurological mutant mice on radial arm maze and active avoidance tasks.

The objectives of the present study are to assess the import of gene-imposed structural alterations on behavioral performance and obtain performance data preliminary to studies of experimental mouse chimera behavior. Reeler, staggerer, and weaver neurological mutant, and control B6C3 and ichthyosis mice were tested on radial arm maze and active avoidance tasks. Weaver mice had incapacitating seizures while performing the radial arm maze task and were, therefore, removed from further testing. Staggerer mice displayed a significant deficit on both tasks compared to control mice. Homozygous reeler mice (rl/rl) also had a significant deficit on the active avoidance task compared to +/rl control mice but not significantly poorer than ichthyosis mice. However, their performance on the radial arm maze task, while initially poor, improved so that they performed the task similar to wild-type controls. Three of the reeler mice reached criterion for solving the radial arm maze task. None of the staggerer mice reached criterion. These data are discussed in terms of the value of using neurologically mutant mice in dissecting structural-functional relationships. It is suggested that the behavior of these mutants might point toward specific components of cerebellar involvement in behavioral acts.

Animals↗
PubMed2005

Novel class of glycosphingolipids involved in male fertility.

Mice require testicular glycosphingolipids (GSLs) for proper spermatogenesis. Mutant mice strains deficient in specific genes encoding biosynthetic enzymes of the GSL pathway including Galgt1 (encoding GM2 synthase) and Siat9 (encoding GM3 synthase) have been established lacking various overlapping subsets of GSLs. Although male Galgt1-/- mice are infertile, male Siat9-/- mice are fertile. Interestingly, GSLs thought to be essential for male spermatogenesis are not synthesized in either of these mice strains. Hence, these GSLs cannot account for the different phenotypes. A novel class of GSLs was observed composed of eight fucosylated molecules present in fertile but not in infertile mutant mice. These GSLs contain polyunsaturated very long chain fatty acid residues in their ceramide moieties. GSLs of this class are expressed differentially in testicular germ cells. More importantly, the neutral subset of this new GSL class strictly correlates with male fertility. These data implicate polyunsaturated, fucosylated GSLs as essential for spermatogenesis and male mouse fertility.

Animals↗