Phenotypic characterization of the KK/HlJ inbred mouse strain.

Detailed histopathological diagnoses of inbred mouse strains are important for interpreting research results and defining novel models of human diseases. The aim of this study was to histologically detect lesions affecting the KK/HlJ inbred strain. Mice were examined at 6, 12, and 20 months of age and near natural death (ie, moribund mice). Histopathological lesions were quantified by percentage of affected mice per age group and sex. Predominant lesions were mineralization, hyperplasia, and fibro-osseous lesions. Mineralization was most frequently found in the connective tissue dermal sheath of vibrissae, the heart, and the lung. Mineralization was also found in many other organs but to a lesser degree. Hyperplasia was found most commonly in the pancreatic islets, and fibro-osseous lesions were observed in several bones. The percentage of lesions increased with age until 20 months. This study shows that KK/HlJ mice demonstrate systemic aberrant mineralization, with greatest frequency in aged mice. The detailed information about histopathological lesions in the inbred strain KK/HlJ can help investigators to choose the right model and correctly interpret the experimental results.

Hippocampal commissure defects in crosses of four inbred mouse strains with absent corpus callosum.

It is known that four common inbred mouse strains show defects of the forebrain commissures. The BALB/cJ strain has a low frequency of abnormally small corpus callosum, whereas the 129 strains have many animals with deficient corpus callosum. The I/LnJ and BTBR T+ tf/J strains never have a corpus callosum, whereas half of I/LnJ and almost all BTBR show severely reduced size of the hippocampal commissure. Certain F1 hybrid crosses among these strains are known to be less severely abnormal than the inbred parents, suggesting that the parent strains have different genetic causes of commissure defects. In this study, all hybrid crosses among the four strains were investigated. The BTBR × I/Ln hybrid expressed almost no defects of the hippocampal commissure, unlike its inbred parent strains. Numerous three-way crosses among the four strains yielded many mice with no corpus callosum and severely reduced hippocampal commissure, which shows that the phenotypic defect can result from several different combinations of genetic alleles. The F2 and F3 hybrid crosses of BTBR and I/LnJ had almost 100% absence of the corpus callosum but about 50% frequency of deficient hippocampal commissure. The four-way hybrid cross among all four abnormal strains involved highly fertile parents and yielded a very wide phenotypic range of defects from almost no hippocampal commissure to totally normal forebrain commissures. The F2 and F3 crosses as well as the four-way cross provide excellent material for studies of genetic linkage and behavioral consequences of commissure defects.

Inherited sperm head abnormalities in the B10.M mouse strain.

Examination of sperm head morphology is one of the requisite tests of the functional capacity of semen in reproduction. In the present study, genetic effects on morphological sperm head abnormalities in mice were investigated. The frequency of abnormal spermatozoa was determined in 17 inbred mouse strains and it was found that strain B10.M had the highest frequency of abnormal spermatozoa (44.7%). Segregation analysis was then used to show that the abnormal sperm phenotype in B10.M mice was inherited. The results indicated that this sperm abnormality was controlled by two distinct recessive alleles. It is proposed that the high frequency of the heritable abnormal sperm phenotype in the mouse B10.M strain explains the subfertility of this strain, as evidenced by its reduced litter size.

Spontaneous exocrine pancreas hypoplasia in specific pathogen-free C3HeB/FeJ and 101/H mouse pups causes steatorrhea and runting.

Under specific pathogen-free conditions, 1.3% to 1.8% of litters born in our inbred 101/H and C3HeB/FeJ mouse colonies had pups with steatorrhea and runting. Clinically affected male and female pups were first identified when they were from 14 to 25 d old. Unaffected littermates were healthy and were weaned successfully. Postmortem findings in 8 clinically affected mice included a small, poorly differentiated exocrine pancreas comprising cytokeratin-negative duct-like structures but lacking recognizable acinar cells with their normal carboxypeptidase B-positive zymogen granules. Endocrine pancreas islets were unremarkable and contained insulin-positive beta cells and glucagon-positive alpha cells. There was mild inflammation of the hindgut but no evidence of intestinal pathogens or marked inflammation or necrosis of pancreas, either alone or as part of a multisystemic inflammatory condition. Sera from pups in 4 affected litters did not contain antibodies to reovirus 3, mouse coronavirus, rotavirus, or mouse adenovirus 2. Furthermore, 4 sets of parental mice and sentinel mice from the facility were negative for 13 viruses, bacteria, and parasites. C3HeB/FeJ and 101/H inbred strains may be genetically predisposed because the steatorrhea and runting was absent in 13 other mouse strains and subspecies bred in the specific pathogen-free facility. This condition resembles exocrine pancreas hypoplasia, but the inheritance is complex. A wider implication is that runting coupled with steatorrhea are phenotypic criteria to suspect pancreatic disease that could be used in the context of a mouse N-ethyl-N-nitrosourea-mutagenesis program to identify potential mutants with defects in pancreas development.

Cloned mice and embryonic stem cell lines generated from adult somatic cells by nuclear transfer.

Mice can now be cloned from cultured and noncultured adult-, fetus-, male-, or female-derived cells. Using the mouse as a model, research is moving towards a comprehensive description of clones generated by somatic cell nuclear transfer. In addition, embryonic stem (ES) cell lines can be generated from adult somatic cells via nuclear transfer (ntES cells). ntES cells contribute to an extensive variety of cell types including neurons in vitro and germ cells in vivo. Recent advances in mouse cloning are reported to illustrate its strengths and promise in the study of mammalian biology and biomedicine.

[Structural abnormalities of hippocampus in 101/HY mice]. / Anomalii stroeniia gippokampa y myshei linii 101/HY.

We studied cytoarchitectonics of the hippocampus in 101/HY and CBA mice on brain sections stained after Nissl and Timm. In CBA mice, the structure of hippocampus was normal. In 10/HY mice, stratum pyramidale in field CA3 was "splitted" and the density of pyramidal neurons was decreased. Abnormalities were also found in the zone of suprapyramidal projections of mossy fibers (sp-ME), i.e., terminals of axons of the fascia dentata granular cells on the apical dendrites of pyramids. If in CBA mice the sp-MF zone was normal, i.e., looked like a vast compact formation or dense ordered bundle, in 101/HY mice, the sp-MF zone represented a group of scattered, diffuse, and interrupted bundles of varying length, some of which were incorporated in stratum pyramidale. Possible causes of the described morphological abnormalities are discussed, as well as their relation to specific features of biology, behavior, and neurological status of 101/HY mice.

Minimal ischaemic neuronal damage and HSP70 expression in MF1 strain mice following bilateral common carotid artery occlusion.

Investigation into the influence of specific genes and gene products upon the pathophysiology of cerebral ischaemia has been greatly enhanced by the use of genetically modified mice. A simple model of global cerebral ischaemia in mouse is bilateral common carotid artery occlusion (BCCAo) and the neuropathological impact of BCCAo has been investigated in several mouse strains. Bilateral carotid occlusion produces extensive neuronal damage in C57Bl/6J strain mice and this damage is linked to posterior communicating artery (PcomA) hypoplasticity in the circle of Willis. In the present study, we investigated the effect of BCCAo in MF1 strain mice and compared them with C57Bl/6J mice. The neuropathological consequences of BCCAo were assessed using standard histochemical staining and heat shock protein 70 (HSP70) immunohistochemical staining (to demarcate cells that had been ischaemically stressed). The effect of BCCAo on mean arterial blood pressure (MABP) was also measured. The plasticity of the circle of Willis was recorded using carbon black perfusion. MF1 mice displayed significantly less ischaemic neuronal damage and HSP70 immunoreactivity compared to C57Bl/6J mice following 10-20 min BCCAo. Moreover, ischaemic neuronal damage and HSP70 immunoreactivity in MF1 mice subjected to extended BCCAo (25-45 min) was never as extensive or widespread as that observed in C57Bl/6J mice after 20 min BCCAo. MABP in MF1 mice (102+/-5 mmHg) was significantly higher than in C57Bl/6J mice (87+/-5) during 20 min BCCAo. MABP in MF1 mice during 20 and 40 min (103+/-12 mmHg) BCCAo remained above pre-occlusion values for the entire occlusion period. MF1 mice had significantly greater circle of Willis plasticity (more PcomAs) than C57Bl/6J mice did. These data indicate that MF1 mice are less susceptible to BCCAo than C57Bl/6J mice and that this could be due to maintained increases in MABP during BCCAo and the lower prevalence of abnormalities of the circle of Willis in MF1 mice.

Effects of the uterine environment and neocortical ectopias upon behavior of BXSB-Yaa+ mice.

Between 40-60% of BXSB-Yaa+mice have neocortical ectopias, a genetically based brain anomaly. The presence of ectopias is known to affect several cognitive measures. A second way to affect cognition is by transferring embryos into foreign uteri. These variables were jointly investigated in three experiments. BXSB-Yaa+mouse embryos were transferred into same-strain uteri, or into uteri of hybrid mice. At birth, pups were cross-fostered to hybrid mothers or were reared by their birth mothers. When adult, the mice were given a series of behavioral tests with primary emphasis upon cognitive competence. Across all three studies, mice transferred into hybrid uteri were superior in the Morris maze and the Lashley III maze, and performed more effectively in shuttlebox avoidance learning. They were less effective in the simple water escape task, and the uterus groups did not differ in discrimination learning. Thus, development within a foreign uterus enhanced spatial learning and fear-based conditioning. Ectopic mice were superior to non-ectopics in learning the Morris maze, a finding consistent with prior research using the congenic BXSB-Yaa strain. There were Uterus x Ectopia interactions on a few measures, indicating that, under certain condition, whether the presence of ectopias is beneficial or detrimental is contingent upon the uterine environment within which the organism develops.