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D Wahlsten

Publications and source records attributed to D Wahlsten.

At least 37 records · Page 2Linked to original sources
PubMed1994

A new hybrid mouse model for agenesis of the corpus callosum.

A three locus model of the inheritance of absent corpus callosum in mice was tested by creating F1 and F2 hybrid crosses from the strains BALB/cWah1 and 129/J which show incomplete penetrance for callosal agenesis. The model predicted that a few of the F2 hybrid mice would suffer severe reduction of the hippocampal commissure when the corpus callosum was absent, a condition that usually occurs only in the most consistently acallosal I/LnJ strain, and this prediction was confirmed. The C129F2 hybrid population expresses substantial genetic variation and an extremely wide range of defects of the corpus callosum, dorsal commissure of the fornix and hippocampal commissure. At the same time, these hybrids have exceptionally good health and reproductive performance, unlike their inbred parent strains. These characteristics make them ideal subjects for the study of brain-behaviour correlation using a noninvasive method.

Agenesis of Corpus Callosum↗
PubMed1994

Retarded growth of the medial septum: a major gene effect in acallosal mice.

Absence of the corpus callosum is a hereditary brain defect that appears with varying severity in four inbred mouse strains and is the result of more than one major genetic locus. If relatively few, perhaps two or three, loci are involved in the prenatal ontogeny of the abnormal corpus callosum, it should be possible to identify a distinct morphological process which shows a major gene effect. Because available evidence suggests the source of callosal agenesis occurs in the substrates of axon guidance near the midsagittal plane rather than in the axons themselves, morphometric analysis was done for sagittal sections of the medial septal region in embryos of normal hybrids and four acallosal strains. The anterodorsal zone of the medial septum subadjacent to the cavum septi grew much slower in acallosal BALB/c and I/LnJ mice whereas the ventral septal region was apparently normal. In the Bailey recombinant inbred strains derived from an acallosal BALB/c progenitor, one recombinant (CXBG/By) closely resembled BALB/c whereas the others resembled the normal C57BL/6 parent strain. This pattern of results supports a major gene influence on fusion of the cerebral hemispheres near the region where the corpus callosum first crosses midplane over the dorsal septum.

Agenesis of Corpus Callosum↗
PubMed1993

Cortical axon trajectories and growth cone morphologies in fetuses of acallosal mouse strains.

Hereditary absence of the corpus callosum (CC) provides an ideal experiment of nature for exploring mechanisms of axon guidance. In this study the prenatal development of CC axons in the acallosal mouse strains BALB/cWah1 and 129/ReJ or J was compared with normal hybrid mice by using the lipophilic dyes DiI and DiA. A few I/LnJ mice were also examined. The time of emergence and growth rate of CC axons from four cortical regions (frontal, parietal, temporal, occipital) were normal in acallosal strains. Their CC axons arrived at midplane on schedule but then often looped back to form the longitudinal Probst bundle. The frequency of formation of the Probst bundle was highest for axons from frontal cortex, which arrived at midplane first, and lowest for occipital axons, which arrived last. Once a few CC axons found a path to the other side via the hippocampal commissure, those that arrived later then crossed relatively normally. Some axons from the Probst bundle also managed to traverse midline in this manner. When no CC axons crossed, almost all of them entered the Probst bundle and eventually left it within a few hours to proceed in the ipsilateral white matter, never turning back toward midplane. Growth cones approaching midplane ipsilaterally and those that had crossed midline and entered contralateral white matter, as well as CC axons in the Probst bundle, expressed a normal range of size and complexity. These results demonstrate that the problem with callosal agenesis resides not in the cells of origin or the axons or growth cones themselves but in the substrates of axon guidance at the midsagittal plane.

Agenesis of Corpus Callosum↗
PubMed1992

Prenatal formation of the normal mouse corpus callosum: a quantitative study with carbocyanine dyes.

Judgment of abnormalities in fetal cortical axon development is more sensitive when a good standard of normal ontogeny is established. The recent availability of postmortem tract tracing methods has greatly improved the observation of axon extension and growth cone morphology in mouse fetuses, which allows much stronger statements about the timing of crucial steps in the formation of the corpus callosum in particular. The first outgrowth and crossing of midplane by axons of the corpus callosum (CC) were examined in 153 normal mouse embryos and fetuses of the hybrid cross B6D2F2/J with carbocyanine dyes applied to brains fixed by perfusion. In most brains a crystal of DiI was inserted into either frontal, parietal, temporal, or occipital cortex in one hemisphere, and a crystal of DiA was placed into a different site in the opposite hemisphere. Although dye diffusion obscured the emergence of axons, linear regression analysis revealed that the first callosal axons emerged from their cortical cells of origin at about 0.4 g body weight or 15.5 days after conception for all four sites. Subsequent axon growth rate was substantially faster for those from frontal cortex (3.2 mm/day) than occipital cortex (1.8 mm/day). Axons from frontal cortex crossed the cerebral midplane first (0.69 g, E16.3), followed by those from parietal (0.74 g), temporal (0.77 g) and occipital cortex (0.92 g, E16.9). Prior to crossing midplane, the pioneering CC axons were usually 200 microns or less in advance of the main bundle, but when they crossed midplane and encountered CC axons growing from homotopic sites in the opposite hemisphere, the pioneering axons were often 0.5 to 2.5 mm ahead of the main bundle. Growth cones were usually large and complex until they had crossed midplane and were thereafter smaller with simple and flat morphologies. The topography of axons in the CC at midplane was organized according to cortical region of origin from the very beginning, when the CC was only a small cap over the hippocampal commissure and dorsal septum. The quantitative results provide a convenient standard for normal callosal development in mice and should facilitate comparative studies.

Animals↗
PubMed1992

Deficient corpus callosum in hybrids between ddN and three other abnormal mouse strains.

The mouse strain ddN from Japan was crossed with three other inbred strains prone to absence of the corpus callosum (BALB/cWah1, I/LnJ and 129/ReJ), and at least one brain with abnormally small corpus callosum was observed in offspring from each F1 hybrid cross. Data for several polymorphic protein markers revealed that the four strains are not closely related genetically. Nevertheless, they share common genetic causes of an absent corpus callosum, which helps to understand why anatomical studies of ddN and BALB/c have yielded similar results. The hippocampal commissure is abnormally small in I/LnJ mice and the anterior commissure is often malformed in BALB/c mice, but both commissures in hybrids were normal, which suggests a different genetic basis for these defects and the absent corpus callosum.

Agenesis of Corpus Callosum↗
PubMed1991

Patterns of cerebellar foliation in recombinant inbred mice.

Morphometric analysis of cerebellar foliation patterns at the midsagittal plane was done in the inbred strains BALB/cByJ, C57BL/6ByJ and their 7 recombinant inbred strains in order to assess possible major gene influences. The cerebellum was dissected away from the brainstem and weighed prior to histology so that measures of the depth of fissures and sulci could be related to overall size of the brain and cerebellum. Results for 177 mice revealed that many brains had extra sulci present within the central lobe, the culmen, the declive and the uvula, and that patterns within a genetically uniform inbred strain were highly variable. The measure of sulcus depth was continuous, showing no evidence of a normal versus abnormal dichotomy. Furthermore, the frequency and depth of extra sulci were greater in mice with larger cerebella. Strain differences in size of the whole brain and cerebellum clearly resulted from several genetic loci. This was also true of the extra sulci, except for the declival sulcus which revealed a single gene influence. The gene symbol 'declival sulcus of cerebellum' (dsc) is proposed.

Animals↗
PubMed1991

The effects of intrauterine position on the degree of corpus callosum deficiency in two substrains of BALB/c mice.

Measures of several intrauterine position variables as well as an index of abnormality of fetal commissure development (z score) were obtained for fetuses of two substrains of BALB mice, BALB/cWah1 and BALB/cWah2, known to differ as adults in the proportion of animals exhibiting deficient corpus callosum (about 55% & 20% respectively). The extent of midline commissure development at embryonic Day 17.5 for most strain 1 fetuses was significantly reduced compared to strain 2 fetuses of the same chronological age. The two substrains also differed with respect to mean litter size and mean body weight (strain 2 greater than strain 1 for both measures). The ovarian and cervical positions for strain 2 uteri were found to be the most favorable for body and placental growth; no such differences were evident in strain 1. In strain 2, fetuses in the left uterine horns showed lower z scores (more retardation) than littermates on the right side, but this difference was not evident in strain 1; no other right/left differences were found in strain 2 which could help to explain the right side advantage. None of the other position variables either separately or in combination was found to be important in predicting the z score index. Tests for randomness failed to provide evidence for nonrandom distribution of severely affected fetuses. We suggest that nongenetic variability resulting from stochastic events early in development and intrinsic to the fetus may be responsible for only certain BALB fetuses within a litter exhibiting the callosal anomaly.

Agenesis of Corpus Callosum↗
PubMed1990

Path analysis of sex difference, forebrain commissure area and brain size in relation to degree of laterality in selectively bred mice.

Male and female mice from HI and LO lines selectively bred by Collins for strength of lateralization were tested for paw preference and then studied histologically to assess size of forebrain commissures and myelination of the corpus callosum. When compared to LO line mice, HI line mice were more strongly lateralized for paw preference and had larger brains as well as greater cross-sectional areas of the anterior commissure and corpus callosum. A substantial sex difference was found only for body size. Myelination of the corpus callosum did not differ consistently between the lines or sexes. Path analysis indicated that the line difference in the anterior commissure was a consequence of the difference in brain size, but corpus callosum size was actually smaller in the HI line than the LO line when brain size was taken into account. However, the size of the corpus callosum relative to brain size was not related to strength of paw preference, whereas brain size relative to corpus callosum size was positively correlated with strength of paw preference. These results support the hypothesis that the large difference in brain size between the Collins HI and LO lines is an important cause of the difference in strength of behavioral lateralization.

Animals↗
PubMed1989

Genetic and developmental defects of the mouse corpus callosum.

Among adult BALB mice fewer than 20% usually have a small or absent corpus callosum (CC) and inheritance is polygenic. In the fetus at the time when the CC normally forms, however, almost all BALB mice show a distinct bulge in the interhemispheric fissure and grossly retarded commissure formation, and inheritance appears to result from two autosomal loci, provided the overall maturity of fetuses is equated. Most fetuses recover from the early defect when the CC axons manage to cross over the hippocampal commissure, and thus there is developmental compensation for a genetic defect rather than arrested midline development. The pattern of interhemispheric connections when the adult CC is very small is topographically normal in most respects, despite the unusual paths of the axons. The proportion of mice which fail to recover completely can be doubled by certain features of the maternal environment, and the severity of defects in adults can also be exacerbated by new genetic mutations which create new BALB substrains. The behavioral consequences of absent CC in mice are not known, nor have electrophysiological patterns been examined. The mouse provides an important model for prenatal ontogeny and cortical organization in human CC agenesis, because these data are not readily available for the human condition.

Agenesis of Corpus Callosum↗
PubMed1989

The quantitative relationship between nutritional effects on preweaning growth and behavioral development in mice.

Our objective was to establish whether nutritional effects on the behavioral development of preweaning mouse pups were linearly related to effects on body and brain growth or whether there was a threshold effect, with behavior being affected only by nutritional extremes. We also used a standardized scale of development to compare the relative magnitude of such effects on morphological and behavioral measures. The level of nutrient availability was manipulated continuously by rearing the pups in litter sizes ranging from 3 to 12. On Day 32 post-conception, measures were taken of body weight, brain weight, thickness of the cerebellar external granular layer (EGL), and behavioral development. The relationship between litter size and body weight, brain weight, and behavioral development was best described by a linear regression model; no threshold effect was apparent. By comparing measures on animals from different litter sizes at the same age (32 days) to standard developmental curves over a wide range of ages, we found that for every additional pup in a litter, body growth was retarded by the equivalent of 1.28 days, brain weight by 0.44 day, and behavioral development by 0.07 day. Although the variation in nutrient availability provided by this range of litter sizes does result in a linear relationship between growth and behavioral development, there is nevertheless considerable sparing of function.

Animals↗
PubMed1989

Deficiency of the corpus callosum: incomplete penetrance and substrain differentiation in BALB/c mice.

In a foundation population of BALB/c mice used to establish a colony at Waterloo in 1977, about 11% of adults showed either total absence or gross deficiency of the corpus callosum. Comparisons between parents and offspring, between progenies of different males, and between 13 separate lines established by full-sib inbreeding showed that variation in the adult corpus callosum reflected a genuine incomplete penetrance in a genetically uniform population. However, after seven generations of inbreeding, a spontaneous change occurred in one line (BALB/cWah 1), resulting in more than 50% of adults with deficient corpus callosum, among which about 20% have complete absence of callosal axons traversing the hemispheres.

Agenesis of Corpus Callosum↗
PubMed1988

Effects of a hybrid maternal environment on brain growth and corpus callosum defects of inbred BALB/c mice: a study using ovarian grafting.

The corpus callosum of many but not all BALB/c mice is either abnormally small or absent. The basis for the defect is hereditary, but the proportion of mice expressing the anomaly can be modified by changing the early environment. The present study investigated the effects of an F1 hybrid maternal environment, which is known to promote better fetal development than an inbred environment, on body and brain growth in BALB/c and on the incidence of the corpus callosal defect. Ovarian follicle cells from BALB/cWah (albino) mice were grafted into pigmented F1 hybrid, BALB/cWah, and pigmented BALB female hosts of comparable age which were subsequently mated to BALB/cWah males. Groups of unoperated BALB/cWah and pigmented BALB dams were included as controls. Data from 111 litters were analyzed. Results showed that BALB mice with F1 mothers had heavier bodies at birth, weaning, and 100 days of age and heavier brains at 100 days than those with either grafted or ungrafted BALB mothers. The effects at birth were evident across all litter sizes (2 to 11), but those at weaning and 100 days were seen only in litters of more than 5 or 6. Neither the F1 hybrid maternal environment nor the grafting procedure itself appeared to influence the incidence or expression of the corpus callosal defect. About 22% of the offspring from each of the three groups (ungrafted BALB, grafted BALB, and grafted F1) showed a defective corpus callosum.

Agenesis of Corpus Callosum↗
PubMed1987

Defects of the fetal forebrain in mice with hereditary agenesis of the corpus callosum.

Inbred BALB/c mice are genetically the same, yet less than half of adults show absent or small corpus callosum. Is this because only a minority has prenatal defects of the sling at the telencephalic midline, or do most fetuses have a defective sling but some are able to form a corpus callosum via some other substrate pathway? This question was addressed by comparing large samples of BALB/c fetuses at 17, 18, and 19 days after conception with a series of normal C57BL/6 and hybrid fetuses matched for body size. At 17 days postconception almost all BALB/c fetuses show an unusual widening or bulge in the interhemispheric fissure anterior to the hippocampal commissure. Furthermore, formation of the hippocampal commissure is greatly retarded, although it eventually attains a normal size in adult mice. At 17 days, when mice of normal strains all have a corpus callosum at midplane, almost every BALB/c fetus lacks the structure, but 1 day later 67% of fetuses show delayed formation of this structure and by 19 days all but 7% of fetuses have some callosal axons crossing the midsagittal plane. Many BALB/c fetuses are able to form a corpus callosum without the benefit of a normal sling. The degree of delay of axon crossing is strongly correlated with the severity of sling defects. An unusually small adult corpus callosum occurs because fetal axons are able to follow unusual pathways and actively compensate for absence of the sling, not because of arrested midline development.

Agenesis of Corpus Callosum↗
PubMed1987

Lasting effects on mouse brain growth of 24 hr postpartum deprivation.

When inbred BALB/c mice were separated from their mother for 24 or 36 hr beginning shortly after birth, growth of the body, whole brain and corpus callosum was almost completely stopped. After being returned to their mother, mice deprived for 24 hr gained weight more slowly than non-deprived littermates over the next 6 days but later showed moderate catch-up growth after weaning at 4 weeks of age. After 55 days of recovery, mice deprived for only 24 hr showed significant reductions in brain weight and size of forebrain commissures compared to littermate controls. Approximately twice as many deprived mice had a corpus callosum that was abnormally small compared to controls. These results demonstrate that a rather brief but severe period of separation from the mother can have lasting effects on brain growth.

Animals↗
PubMed1987

The magnitudes of litter size and sex effects on brain growth of BALB/c mice.

In a sample of 67 litters of genetically uniform BALB/c mice, litter size before weaning, which ranged from 2 to 11 animals, had a strong negative and approximately linear effect on body and brain sizes at 100 days after birth. For both males and females, the difference between litters of 11 and 2 was about 3.7 g body weight and 42 mg brain weight. The difference in brain weights was similar to effects produced by severe protein-calorie undernutrition in the postnatal suckling period. The relationship between body weight and brain weight was approximately linear and the fit was not improved significantly by including a nonlinear term or using the allometric equation. The allometric exponent was approximately .35, which is close to values commonly observed for populations of mice having large genetic variability. Although the slopes of the equations relating brain size to body size were similar for males and females, females had substantially larger brains than their male littermates. When males and females were equated statistically for body weight, the brains of females averaged about 32 mg heavier. Statistical considerations in making these estimates are discussed.

Albinism↗
PubMed1984

Growth of the mouse corpus callosum.

Brains of BALB/cCF inbred mice were examined at 15 ages ranging from 16.5 to 50.5 days from conception and cross-sectional areas of major forebrain fibre tracts at the midsagittal plane were measured. The anterior commissure appeared prior to the corpus callosum (CC), which was first seen at midplane at 17.0 days, and both tracts underwent a very rapid increase in size in the prenatal and early postnatal period, reaching the adult range of size at about 1 week after birth or several days prior to the onset of myelination. The growth spurt of these fibre tracts was much more pronounced than that of whole brain. By comparing BALB/c mice with hybrid mice that always have normal CC, it was found that some BALB/c mice at 18.5 days of age which have very small or absent CC do so because the growth of the whole brain is retarded whereas others have CC that is small for the brain size. Evidence also suggested that many mice with no CC but normal brain size at 18.5 days prenatally do eventually acquire at least a small CC. Observations at 3 postnatal ages of BALB/c mice weighed and marked at birth revealed that the 'runts' with low birth weight, which were presumably retarded prenatally, either die or catch up with mice of normal birth weight and do not have unusually small adult CC.

Animals↗