Embryo cryopreservation and development: facts, questions and responsibility.
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Biomedical subjects
Publications and source records attributed to P Roubertoux.
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The midsagittal area of the corpus callosum expressed as the percentage of the hemispheric surface is smaller in the NZB/BlNJ than in the C57BL/6By inbred strain of mice. We performed a QTL mapping analysis using 284 F2s. Two loci linked to this measure were found: the CCrSQTL1 and CCrSQTL2 at 87 and 67 centiMorgans from the centromere on chromosomes 1 and 4 respectively. The two loci interacted significantly. The total source of genetic variation contributed to 25% of the observed variance.
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The deletion of 3bp at codon positions 2642-2645 (delta 2642) of the gene mutated in Huntington's disease (HD) was analysed on the normal (N) and HD chromosomes of 79 French families affected with HD, and previously typed for the (CAG)n repeats. delta 2642 Polymorphism has been found over-represented on HD chromosomes, the relative risk of HD with the deletion being at a value of 8.26. In this study, the presence of the deleted allele on HD chromosomes increases the (CAG)n number (47.93 +/- 1.80 versus 43.50 +/- 2.78) and decreases the age of onset (41.34 +/- 2.09 versus 36.90 +/- 2.41) in the patients with versus without delta 2642; so the deletion may add to the severity of the disease. Our studies of delta 2642 on N chromosomes confirm that the deletion event occurs on N chromosomes with a (CAG)n allele length at the upper end of the normal size range.
Embryo cryopreservation does not induce clear-cut anomalies at detectable rates, but several mechanisms exist for nonlethal damage during the freeze-thaw process, and the risk of moderate or delayed consequences has not been extensively investigated. In a long-term study including senescence, we compared cryopreserved and control mice for several quantitative traits. Significant differences were seen in morphophysiological and behavioral features, some of them appearing in elderly subjects. Thus, apart from its immediate toxicity, embryo cryopreservation, without being severely detrimental, may have delayed effects. These results, consistent with other findings, question the neutrality of artificial reproductive technologies and draw attention to the preimplantation stages in developmental toxicology.
The copper-zinc superoxide dismutase (SOD-1) gene, located on chromosome 21 and triplicated in Down's syndrome (DS), is suspected to be involved in the neuropathology observed in Alzheimer's disease (AD), DS and physiological aging. In order to explore the effect of an overproduction of SOD-1 in the mouse hippocampus, we investigated the Timm-stained mossy fiber (MF) innervation in the hippocampus of transgenic mice for the human SOD-1 gene (hSOD-1 mice). The results showed a decrease of the MF projection area in the hSOD-1 mice overexpressing the SOD-1 protein. These findings suggest that free radicals could play a role in this particular synaptic loss.
A genetic analysis of differences in reactivity to early exposure of female BALB/cBy and C57BL/6By mice to testosterone was performed using the C x B recombinant-inbred (RI) strains. RI female mice were given a single injection of 1 mg of testosterone propionate on day 4 of life and observed in adulthood in the presence of a male attempting to mate. The latency of the first attack, the number of attacks per minute, the incidence of attack, and tail-rattling were recorded. The strain distribution patterns of the RI strains for all variables is consistent with polygenic correlate of reactivity to neonatal androgenization and is concordant with the heterotic inheritance effect observed in F1's for the latency of the first attack and the number of attacks per minute. The RI strain distribution pattern shows that the genetic correlates of reactivity to early testosterone exposure differ according to the variable studied.
The hyposthesis has been proposed that testosterone is involved in the determination of handedness in man: a high sensitivity to testosterone being associated with left handedness. Handedness in mice is tested according to Collins' paradigm: most mice present either a right or a left paw preference but others are ambilateral. The hypothesis that there is an association between a low neonatal imprinting by testosterone and a strong handedness (right or left) is tested here using Tfm male mice which are testosterone insensitive. Our results confirmed the hypothesis, since Tfm males were as well lateralized as their female siblings and significantly more strongly lateralized than their male siblings not carrying the mutation.
Geschwind and Galaburda (1985, 1985b) have advanced a theory of the development of anomalous dominance and its biological associations. The present article reviews existing literature in an attempt to apply this theory to the study of autism.
Age at Eyelid Opening (AEO) differs in two inbred strains of laboratory mice: NZB and CBA/H. Ovarian transplantation and fostering methods were employed to test for variation of genotypic expression in different environments. (1) A global maternal effect was demonstrated for AEO in parental and F1 pups. (2) AEO of H and N pups is not affected by the parental vs. F1 modification of post-natal maternal environment. (3) The genotype of the mother, via uterine environment, interacts with pup genotype: only the CBA/H strain reacts to the parental vs. F1 modification in uterine environment. (4) A cytoplasmic effect for AEO was successfully replicated. Additional analyses demonstrate that AEO is not cytoplasmically inherited but rather modulated by the cytoplasmic environment.
Newborn mice, like all newborn rodents, are able to emit high frequency signals, in particular when they are put out of the nest. Moreover, it is known that in this situation retrieving behaviors are induced in the foster mother, which are likely to reveal stable differences across inbred strains of mice. The question that arises is whether these differences are causally linked to differences in the pup rate of signalling and/or to the capacity of the females of these strains to perceive them. To provide insights into this question, the behavior of 8 inbred strains of mice was observed: A/J, BALB/c, CBA/H, C57BL/6, C57Br, DBA, NZB and XLII. Pup ultrasonic calls of each of these strains, emitted in the same conditions as a retrieving test, were recorded and tabulated. Auditory sensitivities of females belonging to these strains were determined by auditory evoked potentials recorded in the inferior colliculus. These two variables were analysed in relation to scores of females of these strains on three variables of a retrieving test. Results show that the presence of other factors than auditory cues must be taken into account to describe differences across strains in retrieving performances. This conclusion has been confirmed by results obtained using cross-fostering procedure. Female mice unable to utilize ultrasonic information may use other sensory channels. Furthermore, female mice capable of perceiving ultrasounds may also be able to use different sensory modalities in different situations.
The genetic and environmental bases for differences in rate of development were investigated in 2 inbred strains of mice: C57BL/6By (B) and BALB/cBy (C). Twelve motor responses, aside from individual weight, were used to measure these differences. The Recombinant Inbred Strains method was chosen to perform the genetic analysis. Overdominance is shown to be present in 2 variables alone (eye opening, weight at 10 and 20 days). In most cases, each of the response reflexes was found to be associated with several genes (locomotion, hind limb, crossed extensor, righting, vibrissae placing, bar holding). Differences across strains are associated with one segregating unit for rate of disappearance of the rooting response. This unit is mapped on the part of the 4th chromosome including the loci b and H-21. The strain distribution pattern differs for each sensory motor response, consequently no one general genetic factor of development can be advanced. Maternal effects were found for 4 variables (grasping, fore limb placing, eye opening and weight). For two responses, the F1 pups developing the fastest were reared by mothers from the slowest developing parental strain. As regards this latter finding, the authors hypothesize that mothers differ as to the quality of the environment they furnish to their young and pups differ in their ability to benefit from these environments.
The co-actions of genetic effects and the post-natal maternal rearing environment on the development of weight, 9 reflex responses, and survival have been tested by the cross-fostering method in two inbred mice strains--CBA/H and NZB. Pups of the two strains were not treated differentially by the mothers and experimental handling did not systematically affect pup development. Comparisons of unfostered, infostered, and cross-fostered pups show (1) in 16 cases out of 34, reflex development was affected by the pup strain, and in 10 cases out of 34 by the foster mother strain; (2) survival is only affected by the pup strain; (3) weight development is affected by strain of both the pup and the mother as well as their interactions. The adopted pups' scores were situated outside the range of the two non-adopted groups for certain reflexes as well as for weight. Two non-exclusive hypotheses are proposed: the mother strain can affect pup development (1) either through differences in stimulation provided by the mothers (2) or through differences in milk composition.
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A review of literature leads to the following conclusions: 1) There is a contribution of genetic inheritance to the depressive syndromes observed in affective psychoses. 2) None of the modes of transmission suggested accounts for all cases. 3) The hypothesis of genetic heterogeneity is supported by these facts.
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