Reproduction in mice: liver enlargement in mice during pregnancy and lactation

The mechanism of liver enlargement during pregnancy was investigated in the C57BL/6J strain of mice. The C57BL/6J female exhibited a two-fold increase in liver mass during pregnancy. After the completion of lactation the size of the liver was reduced. Liver growth was accomplished with no increase in hepatocyte number and without an increase in total liver DNA content. During the early stages of liver expansion in pregnant females, DNA synthesis could be turned on by partial hepatectomy. However, during the last few days of gestation DNA synthesis and liver growth in response to partial hepatectomy were inhibited. During lactation this inhibition of growth was maintained, but inhibition of DNA synthesis was partially lifted. DNA synthesis and liver growth in response to partial hepatectomy were normal after the termination of lactation. Because of the limited scope of this investigation the full implications of these findings are not yet certain.     

Reproduction in mice: Behavioral changes induced in female mice by mating

Mated C57BL/6J females experienced in food-motivated maze running were found to make more choices and choose more correctly than virgins. The differences correlated with the receipt of spermatozoa and prior pseudopregnancy. Pregnancy, active pseudopregnancy, and male-female social interactions did not appear to be required determinants. The biologic ramifications of mating in mice may extend beyond the fusion of sperm and egg and the induction of hormonal changes that regulate the earliest stages of pregnancy.     

Cocaine kindling in mice

Previous studies proposed the involvement of theN-methyl-D-aspartate (NMDA) type of glutamate receptors in the development of sensitization to the convulsive effect of cocaine (cocaine kindling). The present study was undertaken to determine, first, if cocaine kindling is associated with enhanced sensitivity of the NMDA receptor to the convulsive response ofN-methyl-D,L-aspartate (NMDLA), and second, whether in vivo modulation of nitric oxide synthase (NOS) function regulates the development of cocaine kindling. The following results were observed:

1. Cocaine-kindled animals were significantly more susceptible to the convulsive effect of the NMDA receptor agonist NMDLA than saline controls;
2. Pretreatment with the NOS inhibitor N^G-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg; ip) blocked the development of cocaine kindling;
3. The protective effect of L-NAME was partially reversed with the coadministration of the NOS substrate,L-arginine (300 mg/kg; ip), but notD-arginine; and
4. L-Arginine (300 mg/kg; ip), but notD-arginine, amplified the development of cocaine kindling. Taken together, these findings suggest that supersensitivity of the NMDA receptor and activation of NOS may underlie the development of cocaine kindling.

     

Behavioural homeostasis in mice

For quantitative behavioural traits, hybrids from crosses between inbred strains of mice often show less variability than the inbred strains themselves. Such hybrids therefore show behavioural homeostasis compared with the inbred strains. In some cases behavioural homeostasis is associated with heterosis.     

Conditional RNAi in mice

RNA interference (RNAi)-mediated gene knockdown has developed into a routine method to assess gene function in cultured mammalian cells in a fast and easy manner. For the use of RNAi in mice, short hairpin (sh) RNAs expressed stably from the genome are a fast alternative to conventional knockout approaches. We developed a strategy for complete or conditional gene knockdown in mice, where the Cre/loxP system is used to activate RNAi in a time and tissue dependent manner. Alternatively doxycycline controlled shRNA expression vectors can be used for conditional gene silencing. Single copy RNAi constructs are placed into the Rosa26 locus of ES cells by recombinase mediated cassette exchange and transmitted through the germline of chimeric mice. The shRNA transgenic offspring can be either directly used for phenotypic analysis or are further crossed to a Cre transgenic strain to activate conditional shRNA vectors. The site specific insertion of single copy shRNA vectors allows the expedite and reproducible production of knockdown mice and provides an easy and fast approach to assess gene function in vivo.     

Modelling melanoma in mice

Phenotypic and molecular heterogeneity in human melanoma has impaired efforts to explain many of the clinically important features of melanoma. For example, many of the underlying mechanisms that might predict age-of-onset, time to metastasis and other key elements in melanoma progression remain unknown. Furthermore, melanoma staging used to predict outcome and treatment has not yet moved beyond a basic phenotypic classification. While molecularly targeted therapies show great promise for melanoma patients, establishing accurate animal models that recapitulate human cutaneous melanoma progression remains a priority. We examine the relevance of mice as models for human melanoma progression and for key molecular and histopathologic variants of melanoma. These mice may be used as preclinical models to probe the relationships between causative mutations, disease progression and outcome for molecularly targeted therapeutics. We ask how new mouse models, or more detailed histopathologic and molecular analyses of existing mouse models, may be used to advance our understanding of genotype-phenotype correlations in this tumour type. This necessarily involves a consideration of the utility of mice as models for ultraviolet radiation-induced melanoma, and how this might be improved.     

Megaoesophagus in ICRC mice

The occurrence of megaoesophagus in ICRC/HiCri mice afforded opportunities to study the genetics and histology of this condition. The anomaly was found to be inherited as a recessive character. Histology indicated abnormality in the myenteric plexus.     

Somatostatin mydriasis in mice

Administration of somatostatin intracerebroventricularly to mice produced a dose-dependent mydriasis, whereas intravenous injections were ineffective. Naloxone could prevent or abolish this effect. It is suggested that somatostatin either directly excites opiate receptors or activates endopioid pathways involved in the regulation of pupillary size.     

Dispersal in house mice

This review evaluates direct (live-trapping) and indirect (genetic) methods to study dispersal in wild house mice ( Mus musculus ) and summarizes field and experimental data to examine the causes and consequences of dispersal. Commensal house mice (associated with human habitations, farms, food stores and other anthropogenic habitats) typically show lower rates of dispersal than feral house mice (living in crops, natural and semi-natural habitats). However, early claims of long-term fine-scale genetic structure in commensal house mice (due to low rates of dispersal) are not supported by recent data. Dispersal becomes obligatory when habitat conditions deteriorate, but most dispersal occurs below the local environmental carrying capacity and is due to social interactions with conspecifics. Excursions are relatively frequent and probably allow mice to assess the quality of habitats before dispersing. Young males have the greatest tendency to disperse, apparently prompted mainly by aggressive interactions with dominant males. If they do disperse, females integrate into new groups more easily than do males. Dispersing house mice risk loss of condition or death, but may gain reproductive opportunities on arrival in a new location. House mice can be transported passively as stowaways with humans; this contributes to population persistence and genetic structure at regional scales and has allowed house mice to spread world-wide.  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 565–583.     

Stress hyperthermia in mice

1. 1.|Colonic temperature (T_c) of mice rose about 2°C in 20 min when the mice were taken out of their home cages and the T_c measured every 5 min.

2. 2.|The maximal rise in T_c diminished if the procedure was repeated daily for 43 days and increased abruptly again when the T_c measurements were taken, in one session, in the presence of a rat.

3. 3.|Salicylate diminished the maximal T_c but not the difference between the maximal and the initial T_c, i.e. the magnitude of the T_c rise.

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Mutagenicity tests in mice

Summary The dominant lethal method has been described and the control data of C3H inbred mice and (101xC3H)F₁ hybrids were analysed. It could be demonstrated that infectious diseases and the number of implantations per uterus can influence the embryonic mortality. Other tested parameters such as 0.9% NaCl solution, aqua dest., and paternal and maternal age have within a certain frame no effect on the embryonic mortality. The heterogeneity does not permit a pooling of the controls and suggests on the other hand that each experiment should have a sufficient number of own controls to enable a decision over the mutagenicity of a compound.(Direktor: Prof. Dr. F. Vogel)