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Biomedical subjects

D Wahlsten

Publications and source records attributed to D Wahlsten.

At least 55 records · Page 3Linked to original sources

Maternal effects on mouse brain weight.

When BALB/cCF mice were crossed reciprocally with 4 other inbred strains, adult brain weights averaged 21.0 mg heavier for hybrid offspring with a BALB mother than those with a BALB father. Reciprocal backcrosses to BALB revealed that this effect was a consequence of the BALB maternal environment, not cytoplasmic or sex chromosomal influences. These findings demonstrate that BALB mice have heavier brains than those of several other inbred strains, partly because of chromosomal influences, but also because of their maternal environment, an environmental influence which usually functions as a component of heredity in studies comparing inbred strains. Backcrosses also revealed a maternal environment effect whereby offspring with an F1 hybrid mother had adult brains averaging 9.0 mg heavier than those with a BALB mother.

Animals↗

Axonal guidance during development of the great cerebral commissures: descriptive and experimental studies, in vivo, on the role of preformed glial pathways.

Do structures exist within the embryonic central nervous system that guide axons across the midline during development of the great cerebral commissures (corpus callosum, anterior commissure)? With the use of serial section and reconstructive computer graphic techniques we have found that during normal ontogeny of the mouse forebrain and before the arrival of the pioneer fibers of the corpus callosum at the midline, a population of primitive glial cells migrates medially (through the fused walls of the dorsal septum) from the ependymal zones of each hemisphere. At the midline, and well rostral to the lamina terminalis, these cells unite to form a bridgelike structure or "sling" suspended below the longitudinal cerebral fissure. The first callosal axons grow along the surface of this cellular bridge as they travel toward the contralateral side of the brain. The "sling" disappears neonatally. The fibers of the anterior commissure grow within the lamina terminalis along a different type of preformed glial structure. Movement of these axons occurs through an aligned system of glial processes separated by wide extracellular spaces. Do these transient glial tissues actually provide guidance cues to the commissural axons? Analyses of three situations in which the glial "sling" is genetically or surgically impaired or nonexistent indicate that this structure does, indeed, play an essential role in the development of the corpus callosum. We have analyzed (1) the embryonic stages of a congenitally acallosal mouse mutant (strain BALB/cCF), (2) several pouch stages of a primitive acallosal marsupial, Didelphys virginiana (opossum), and (3) animals in which the "sling" had been lesioned surgically through the uterine wall in the normal embryo (strain C57BL/6J). In the acallosal mouse mutant fusion of the septal midline is delayed by about 72 hours and the "sling" does not form. Although the would-be callosal axons approach the midline on schedule, they do not cross. Instead, the callosal fibers whirl into a pair of large neuromas adjacent to the longitudinal fissure. Similarly, in the opossum, fusion of the medial septal walls and formation of the glial "sling" are also lacking. However, in this species, instead of traveling dorsally, the "callosal" axons turn ventrally and pass contralaterally by way of the anterior commissure pathway. Surgical disunion of the glial "sling" also resulted in acallosal individuals. The callosal pathology in these affected animals mimicked exactly that of the genetically lesioned mutant. Our observations suggest that many different types of oriented glial tissues exist within the embryonic neural anlage. We propose that such tissues have the ability to influence the directionality of axonal movements and, thereby, play a crucial role in establishing orderly fiber projections within the developing central nervous system.

Agenesis of Corpus Callosum↗

Deficiency of corpus callosum varies with strain and supplier of the mice.

Six inbred strains of adult mice either obtained from commercial suppliers or bred in the author's laboratory at Waterloo were assessed for size of body, brain and corpus callosum (CC) at a wide range of ages. Because almost all measures varied significantly with age, a simple regression procedure was used to minimize age effects statistically. The strains A/J, C57BL/6J and DBA/2J differed substantially in brain size and size of CC, but none of these animals ever showed severe deficits of CC fibres crossing the midsagittal plane. For these 3 strains the sizes of body, brain and CC were larger when bred at the Jackson Laboratory than at Waterloo. Two BALB/c strains obtained from different suppliers had over 30% of mice with defective CC, ranging continuously from total absence of transcortical fibres to slightly reduced CC size. For these two strains bred at Waterloo, brain sizes were larger and CC defects were much less frequent than when bred by commercial suppliers. The strain 129/J had a 71% frequency of CC defects when reared at the Jackson Laboratory but 38% defects when bred and reared at Waterloo. However, bodies of 129/J mice bred at Jackson were larger than those bred at Waterloo. These results show that relatively small differences in rearing conditions can have relatively large effects on certain aspects of brain development.

Agenesis of Corpus Callosum↗

Mice in utero while their mother is lactating suffer higher frequency of deficient corpus callosum.

Mice of the inbred strain BALB/cCF which were conceived during the post-partum estrus and developed in utero while their mother was nursing a previous litter had twice the frequency of agenesis or deficiency of corpus callosum as their close relatives which did not overlap with another litter. There was no harmful effect of overlapping litters on body or whole brain size, so the phenomenon must have resulted from some aspect of maternal environment other than quantity of nutrition.

Agenesis of Corpus Callosum↗

Prenatal schedule of appearance of mouse brain commissures.

Different inbred mouse strains and hybrid crosses develop at different rates prenatally, but when brains of fetuses with the same extent of external morphological maturity are compared, a very precise schedule of appearance of major fibre tracts at the mid-sagittal plane is apparent. Using fetuses ranging in age from 13.0 to 18.0 days, the general order or arrival of fibre tracts at midplane is: posterior commissure, optic chiasm, stria terminalis, habenular commissure, columns of the fornix, anterior commissure, hippocampal commissure and corpus callosum. The corpus callosum crosses midplane at least one full day after the other fibre tracts, and it crosses just dorsal to the hippocampal commissure. The data suggest that the interhemispheric fibres from neocortex which are prevented from crossing midplane in some BALB/c mice do not find an alternative pathway via the anterior commissure, as they do in many marsupials with no corpus callosum, because the anterior commissure forms about two days before the callosal fibres normally cross midplane and is relatively mature when the callosal fibres are diverted away from midplane.

Animals↗

Precision stereotaxic procedure for the mouse (Mus musculus): method and instrumentation.

A precision stereotaxic procedure for mouse brain research is described accompanied by a new design in mouse stereotaxic head holder and a new device used to guarantee accurate alignment of the skull in the stereotaxic device. This method and instrumentation when applied in forthcoming research will contribute to the development of investigations of structure/function relationship in mouse brain.

Animals↗

Implications of genetic variation in mouse brain structure for electrode placement by stereotaxic surgery.

The spatial locations of several forebrain and midbrain fibre tracts have been compared across seven commonly used inbred, hybrid and outbred mouse strains using a series of electrolytic lesions of known positions with respect to a stereotaxic instrument. Highly significant genetic variation was found in the position of lambda, bregma and several major fibre tracts with respect to interaural zero; in the locations of fibre tracts with respect to bregma; and in the location of fibre tracts with respect to each other. It was demonstrated that stereotaxic coordinates of a structure for one strain could not be used for other strains. Errors resulting from improper alignment of the head in the instrument and histological artifact were also determined. These errors showed no significant group differences, but they revealed that within-group variation was substantially affected by such imperfections.

Animals↗

Genetic variation in the development of mouse brain and behavior: evidence from the middle postnatal period.

Six inbred strains and 3 F2 hybrid crosses of mice were assessed for developmental status at 32 days after conception (about 13 days after birth). Phenotypes measured included body weight, brain weight, maturity of 14 reflexive behaviors, myelination of 80 fiber tracts, and thickness of the external granular layer of the cerebellum. All measures of brain and behavior showed a similar pattern of results: hybrids were generally more advanced than either of their inbred parent strains; differences among inbred strains were large, but differences among hybrid crosses were quite small. Acceleration of F2 mice compared to their homozygous relatives ranged from .5 to 2.4 days mean difference. Developmental ages of inbred litters ranged from 28.7 to 32.2 days, whereas hybrid litters ranged from 31.5 to 32.7 days.

Animals↗

Heritable aspects of anomalous myelinated fibre tracts in the forebrain of the laboratory mouse.

Serial coronal or sagittal sections were stained for myelin and examined in 6 inbred, 4 hybrid, and 2 outbred mouse strains. Absent corpus callosum was seen only in BALB/cJ as reported by Wimer, but a wide range of the size of corpus callosum was also noted. The action of a major gene was not evident in backcross or F2 generations; polygenic and perhaps epistatic inheritance was indicated. In A/J, and to a lesser extent A/HeJ and BALB/cJ, the columns of fornix frequently collided with the anterior commissure and either passed around it to make a normal termination or deflected dorsally to make an abnormal termination in lateral septum. In some BALB/cJ brains the anterior commissure instead was displaced and passed behind or through the columns of fornix. Backcross and F2 data suggested inheritance was polygenic and that genetic variation affected the spatio-temporal coordination of ontogeny of the two tracts. Finally, unusual longitudinal bundles were detected in the septal region of BALB/cJ. Results of crosses were consistent with the hypothesis that a single, incompletely dominant gene was acting, but further study of both the anatomy and heredity of the defect was deemed necessary.

Agenesis of Corpus Callosum↗