Cadmium-induced forelimb ectrodactyly: a proposed mechanism of teratogenesis

We have attempted to elucidate the mechanism of cadmium teratogenesis utilizing inbred mouse strains sensitive (C57BL/6J) or resistant (SWV) to the embryotoxic effect of this common heavy metal contaminant. Carbonic anhydrase activity of whole-embryo homogenates was moderately depressed in C57BL/6J mice compared to a slight and transient decrease in the resistant SWV mice. Embryonic erythrocytes were similarly examined, and the cadmium did not have any effect on carbonic anhydrase activity in either strain. Likewise, histochemical examination of carbonic anhydrase activity did not reveal any effect of cadmium in the embryos of their strain. Generally, the zinc concentration of embryos was not affected by cadmium administration. However, increased levels of zinc were observed in cadmium-exposed yolk sacs of both strains suggesting that cadmium produces an adverse effect on yolk sac function. Untreated C57BL/6J units (embryo plus surrounding extraembryonic membranes), embryos, and yolk sacs had much lower hemoglobin concentrations than those observed in untreated SWV units, embryos, and yolk sacs. Additionally, cadmium exposure significantly decreased C57BL/6J embryonic hemoglobin levels on gestation day 10 (PM) and increased C57BL/6J yolk sac hemoglobin levels on gestation days 10 (AM) and 10 (PM). No difference in hemoglobin concentration was observed between untreated and cadmium-treated SWV embryos or yolk sacs. We propose that cadmium induces forelimb ectrodactyly by creating an acidotic embryonic environment and that the primary site at which cadmium exerts its teratogenic effect might be the yolk sac.     

Dose-response relations of palatal slit, cleft palate, and fetal mortality in mice treated with a glucocorticoid

C57BL/6 (C57BL) and SWV mice were treated subcutaneously with triamcinolone acetonide in a single dose of 1.0-7.0 mg/kg on day 12 of pregnancy, and the palate of their fetuses was examined at term. In C57BL mice palatal slit occurred spontaneously and its frequency increased with increasing doses of triamcinolone. However, this defect was not seen in SWV fetuses, even when dams were treated with the doses that induced cleft palate. The frequency of cleft palate increased in both C57BL and SWV as the dose of triamcinolone increased. Fetal mortality increased in SWV, but not in C57BL, with increasing doses of triamcinolone. Dose-response relations were analyzed by the log-probit transformation method. In C57BL mice, the slope of the dose-response curve of palatal slit was significantly different from that of cleft palate. In contrast, the dose-response curves of cleft palate were similar in both C57BL and SWV; the median effective dose was significantly greater in C57BL than in SWV. The mechanism of induced palatal slit appears to be different from that of induced cleft palate; the mechanism of cleft palate induction may be the same in both C57BL and SWV. The slope of the dose-response curve of fetal mortality in SWV mice was different from that of cleft palate; the mechanisms underlying the resorption and cleft palate responses must be different.     

Strain differences between C57BL/6 and SWV mice in time of palate closure and induction of palatal slit and cleft palate

Palatal slit, which occurs spontaneously in C57BL/6 (C57BL) mice, is increased in frequency among C57BL fetuses from dams treated with triamcinolone acetonide, but is not induced in SWV fetuses. On the other hand, C57BL is more resistant than SWV to cleft palate induction by triamcinolone. Using these C57BL and SWV mice, the relation of palate stage and chronological age was examined from 1 P.M. on day 14 to 9 A.M. on day 16 in untreated embryos, and the condition of the palate after triamcinolone treatment on day 12 was examined at 9 A.M. on day 16. In untreated embryos, horizontalization and fusion of the palatal shelves occurred earlier in C57BL than in SWV embryos, but fusion of the primary palate with the secondary palate occurred later. After triamcinolone treatment, the development of the palate was delayed in both C57BL and SWV embryos. These results suggest that the times of normal palate closure are related to the differences between C57BL and SWV mice in their susceptibilities to palatal slit and cleft palate induction and that triamcinolone produces palatal slit and cleft palate by delaying palate closure.     

Occurrence of cleft palate, palatal slit, and fetal death in mice treated with a glucocorticoid: an embryo transfer experiment

SWV and C57BL/6 (C57BL) mice were treated subcutaneously with triamcinolone acetonide in a single dose of 2.5 mg/kg on day 12 of pregnancy (vaginal plug = day 0), and the palate of their fetuses was examined at term. Cleft palate was seen in some SWV and C57BL fetuses; its frequency was significantly higher in the former. Closer examination revealed palatal slit in some C57BL, but in no SWV fetuses. In addition, fetal mortality was significantly increased in SWV, but not in C57BL, exposed to triamcinolone. These strain differences in cleft palate, palatal slit, and fetal mortality were investigated by embryo transfer. The results showed that, in cleft palate induction, the effects of uterine environment were more important than those of fetal genotype. On the other hand, after transfer, palatal slit still occurred in C57BL but not in SWV fetuses; thus, in palatal slit occurrence, the fetal genotype played a more important role than the uterine environment. Accordingly, it is suggested that the nature of the participation of fetal genotype and uterine environment in palatal slit occurrence is different from that in cleft palate induction. In regard to fetal mortality, embryo transfer procedures influenced it in SWV dams and the effect of triamcinolone could not be detected after embryo transfer.     

不同品系小鼠胚胎玻璃化冷冻保存的比较研究

目的　研究甘油作为冷冻保护剂、不同基因型小鼠对胚胎玻璃化冷冻的影响。方法　采用 6 5mol L的甘油作为冷冻保护剂 ,采用二步法对CBA、NOD、C57BL 6J、ICR及CD1小鼠 3 5d的胚胎进行玻璃化冷冻 ,并比较了不同品系小鼠胚胎的复苏率及移植受孕率。结果和结论　CBA、NOD、C57BL 6J,ICR及CD1的复苏率分别为 5 7 6 %、4 8%、31 3%、86 5 %及 88% ,移植受孕率为 2 1%、2 3 5 %、11%、38%和 35 5 % ,封闭群小鼠的胚胎复苏率、移植受孕率均显著高于近交系小鼠。这提示胚胎的复苏率及移植受孕率可能与小鼠的不同基因型有关。五个品系中 ,桑椹胚及早期囊胚的体外复苏率均显著高于扩张囊胚。这说明不同基因型及胚胎的不同发育阶段对胚胎玻璃化冷冻效果有影响     

Developmental responses of two substrains of in vitro fertilized C57BL/6J mouse embryos to oxygen and amino acids.

The developmental response of in vitro fertilized embryos to oxygen and amino acids were compared between in-house bred C57BL/6JNrs (Nrs) and commercially available C57BL/6JSlc (Slc) mice. Under 20% oxygen, the percentage of embryos that developed to blastocysts and expanded blastocysts, and nuclear numbers were lower in Slc embryos than in Nrs embryos. Moreover, the nuclear number did not increase in Slc embryos during 72-96 h culture. Effects of amino acids were beneficial on development of Slc embryos under 20% oxygen, but inhibitory on blastocoel formation at 78 h under 5% oxygen. On the other hand effects of amino acids on Nrs embryos were observed in nuclear number at 72 and 78 h culture under 5% oxygen. Because the present study showed differences in sensitivity to culture conditions between the C57BL/6J substrains, care must be taken in embryo manipulation of this inbred strain in studies of embryo development or other studies.     

Effects of dexamethasone on phospholipase activities in palate mesenchyme cells in vitro

Treatment of primary cultures of palate mesenchyme cells from AJAX strain embryos with dexamethasone inhibited only phospholipase activity expressed at pH 7.5. A similar treatment did not have such an effect on palate mesenchyme cells from C57BL/6J strain embryos. Since the AJAX strain embryo is sensitive to the induction of cleft palate by exogenous glucocorticoids and the C57BL/6J strain is less so, these data allow consideration of phospholipase activity as a site of regulation for development of the palate.     

Apoptosis in the preimplantation mouse embryo: effect of strain difference and in vitro culture.

Cell death by apoptosis occurs predominantly in the inner cell mass (ICM) of the blastocyst, the cell population which carries the germ line and gives rise to the foetus. The frequency of apoptosis in blastocysts varies widely within outbred species such as human and cow. We have addressed the basis of this variation by examining the relative influence of strain difference and in vitro culture conditions on apoptosis, using embryos from two different strains of mice (MF1 and C57BL6/CBA) in two different culture media (M16 and kSOM). In both strains and all crosses apoptosis was first detected by nuclear fragmentation or TUNEL [Terminal deoxynucleotidyl transferase mediated d-UTP nick end-labelling] labelling at the early blastocyst stage. This was true for embryos which had developed in vivo, and in vitro in both M16 and kSOM. The apoptotic index in blastocysts was found to be significantly different between both media and strain (P < 0.0001). Blastocysts from MF1 x MF1 at equivalent stages had an apoptotic index of 32.4% in M16 and 20.3% in kSOM. Blastocysts from C57BL6/CBA x C57BL6/CBA had an apoptotic index of 19.3% in M16 and 14.4% in kSOM. When embryos of similar cell number were compared, a significantly greater apoptotic index was found for cultured MF1 x MF1 embryos with a cell number between 40 and 59 compared to similar directly flushed C57BL6/CBA embryos (P = 0.001), and MF1 embryos (P < 0.0005). MF1 x MF1 embryos and C57BL6/CBA x MF1 embryos of 60-79 cells had a greater apoptotic index in M16 than kSOM (P < 0.0005) but the difference between media was not significant for C57BL6/CBA x C57BL6/CBA. When strain was compared MF1 x MF1 embryos of 60-79 cells had a significantly greater apoptotic index than C57BL6/CBA x MF1 in both media (P < 0.0005 M16; P = 0.002 kSOM) and than C57BL6/CBA x C57BL6/CBA in M16 (P = 0.019). Our data suggest that genetic make-up and the chemical composition of simple medium are equally important in determining the level of apoptosis.     

Genetic analysis of spontaneous and induced palatal slit in C57BL/6 mice

The results of experiments designed to elucidate the nature of the genetic factors underlying the palatal slit defect in C57BL/6 mice indicate that probably two loci in females and four in males determine the difference in susceptibility to the spontaneous defect between the C57BL/6 and SWV/BcTa strains of mice. Moreover, it appears that these are not the same genes determining the difference between these same strains in palatal slit response to maternal treatment with triamcinolone. Additional evidence is presented to support the view that in the C57BL/6 strain the triamcinolone-induced palatal slit and cleft palate responses are not correlated.     

Chloride transport in embryonic cells: effect of ethanol and GABA

Ethanol and GABA (gamma-aminobutyric acid) and their interaction on 36Cl-influx were analyzed in cultured embryonic palate and limb mesenchymal cells in order to determine whether ethanol exerts its teratogenic action through a GABA receptor involved in embryogenesis. Cl- transport in secondary cultures of C57BL/6 palate mesenchymal cells was shown to consist of three systems including the electroneutral Cl-/HCO3- exchange (50%) and Na+/K+/Cl- cotransport (30%) pathways and the voltage-dependent Cl- channel (20%). Treatment with DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) or SITS (4-acetamido-4'-isocyano-stilbene-2,2' disulfonic acid) in SWV palate cells inhibited the Cl-/HCO3- exchange pathway, while treatment with DIDS and bumetanide inhibited both the exchange and cation cotransport pathways, the residual Cl- influx inferred to be the electrogenic pathway. Inhibition of Cl- transport by anthracene-9-carboxylic acid confirmed the presence of the electrogenic Cl- pathway. It was observed that the rate of Cl- transport was significantly greater in palate cells of C57BL/6 mice than those of SWV mice. Also the rate of Cl- transport was significantly greater in secondary cultures of palate cells from C57BL/6 mice than from primary cultures of limb cells from the same strain. No evidence could be obtained that ethanol (10 to 100 mM) or GABA (3 X 10(-5) M) or their combination stimulated total Cl- influx in either C57BL/6 or SWV palate mesenchymal cells, putative voltage-dependent Cl- influx in C57BL/6 palate cells, or total Cl- influx in primary cultures of C57BL/6 limb mesenchymal cells.     

The development of the hemopoietic system: colony-forming splenic units in mouse embryogenesis

Localization and time of appearance as well as dynamics of quantitative changes of splenic colony-forming units (CFU-S) in mouse (C57BL/6 X CBA)F1 embryos were studied. Cells taken from the whole embryo (day 8), yolk sac and embryo per se (day 9), and also liver (day 10) were injected into the lethally irradiated syngenic mice. 7-8 days after the injection the spleens were fixed and the number of macrocolonies was counted. Statistically significant number of CFU-S was detected starting from day 10 of development, first in the embryo (30-33 somites), then in yolk sac and blood (37-38 somites) and liver (after the 40 somites stage). Rapid increase of CFU-S number during days 11-12 (two-fold increase in about 4.6 hours) suggest that not only active proliferation of CFU-S but also maturation of CFU-S precursors take place.     

The genotypic response of mouse embryos to multiple freezing variables

Four- and eight-cell embryos from 3 mouse genotypes were cryopreserved to study the relationship of genetics and freezing variables on post-thaw survival. Embryos from outbred N:NIH(S), N:NIH(S)-B and inbred (C57BL/6N) mice were exposed to 1 of 2 cryoprotectants (glycerol [GLYC] versus dimethyl sulfoxide [DMSO]) and stored in 1 of 2 containers (ampules [AMP] versus straws [STR]). Containerized embryos were cooled at a rate of 0.5 degrees C/min to a minimum of -35 degrees C, transferred into liquid nitrogen, and later thawed and cultured in vitro. Genotypic differences (p less than 0.05) were noted for 4 interrelated embryo characteristics including post-thaw survival (PTS), embryo degeneration rate (EDR), and quality grade (QG) and viability grade (VG) ratings. The PTS for outbred embryos was greater (p less than 0.05) in GLYC than DMSO, whereas inbred C57BL/6N embryos survived similarly (p greater than 0.05) in either cryoprotectant. Compared to DMSO counterparts, embryos from GLYC-treated outbred groups had improved QG and VG ratings and reduced EDR (p less than 0.05), but comparable results were observed between GLYC- AND DMSO-treated embryos in the C57BL/6N group. Between genotypes, type of container affected PTS and EDR (p less than 0.05) but not QG or VG ratings (p greater than 0.05). Within genotypes, PTS generally ranged 15 to 20% higher (p less than 0.01) in AMP than STR groups. Increased PTS was noted in outbred mouse x GLYC x AMP groups; however, based on the degrees of difference, the inbred C57BL/6N strain appeared less affected by this 3-way interaction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Viability of frozen-thawed mouse embryos is affected by genotype

Embryos from mice of five different genotypes were evaluated for their ability to survive cryopreservation as measured by post-thaw in vitro development. In Study 1, ovulation was induced with a standardized pregnant mares' serum gonadotropin (PMSG)/human chorionic gonadotropin (hCG) regimen, after which females were mated with males of the same genotype to produce incrossed embryos. Four- to 8-cell embryos were frozen in 1.5 M dimethyl sulfoxide (DMSO) at a rate of 0.5 degrees C/min to -80 degrees C and stored in liquid nitrogen. Following thawing at room temperature, embryos were cultured and development was evaluated 24 h later. The mean (+/- SEM) number of 4- to 8-cell embryos/pregnant female by stock/strain were: N:NIH(S), 6.8 +/- 0.8; N:NIH(S)-B, 5.8 +/- 0.5; N:GP(S), 6.5 +/- 0.6; C57BL/6N, 9.7 +/- 1.0; C3H/HeN MTV-, 9.5 +/- 0.9 (P less than 0.05). Post-thaw in vitro development was related to genetic background; the proportion of embryos culturing after thawing was: N:NIH(S), 49%; N:NIH(S)-B, 61%; N:GP(S), 66%; C57BL/6N, 75%; C3H/HeN MTV-, 56% (P less than 0.05). Study 2 was conducted to evaluate the influence of mating various females to males of a genotype known to have a lower post-thaw embryo survival rate. N:NIH(S)-B, N:GP(S), C57BL/6N, and C3H/HeN MTV- female mice were mated with N:NIH(S) males to produce hybrid embryos. Post-thaw embryo survival was reduced (P less than 0.05) in three of the four hybrid groups. Fresh incrossed and hybrid embryos from each study were cultured for 24 h and yielded culture rates ranging from 95% to 99% (P greater than 0.05) among all groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

小鼠不同阶段胚胎玻璃化冷冻保存的比较研究

The cryopreservation of different embryo stages collected from ICR, C57BL/6 and F1 of DBA*C57BL/6 was carried out by using vitrification method. The morphology, in vitro development and birth rates of these embryos were compared after frozen-thawed. The results showed that more than 75% of the morphology from 2-cell embryos to morula stages from different strains was normal, the normal morphology rates of 8-cell embryos being the highest, while those of blastulas being the lowest. The in vitro development rates became higher as the embryos developed. The morphology of in vivo and in vitro fertilized frozen 2-cell embryos showed no difference, but the development rate of in vivo fertilized frozen 2-cell embryos was significantly higher than that of in vitro ones. Embryos that underwent 3 times frozen-thawing remained normal morphology. The pregnant rate and birth rate of frozen 2-cell embryos after embryo transfer were 64% and 40% respectively, but lower than those of fresh 2-cell embryo transfer.     

小鼠不同阶段胚胎玻璃化冷冻保存的比较研究

采用玻璃化冷冻法对ICR、C57BL/6、DBA~*C57BL/6杂交F1代三种品系小鼠的不同阶段胚胎进行冷冻保存,比较胚胎解冻后形态良好率、体外发育率和移植后的出生率,结果表明解冻后各品系小鼠胚胎从2细胞到桑椹胚形态良好率在75%以上,其中8细胞胚胎形态良好率在83%以上,而囊胚的形态良好率仅在40%左右。解冻后胚胎体外培养的发育率随胚胎发育阶段的提高而提高,桑椹胚的发育达93%以上。体外受精2细胞冷冻胚与体内受精2细胞冷冻胚比较,二者形态良好率差异无显著意义(74%∶75%),但体内受精冷冻胚的发育率明显高于体外受精冷冻胚(76%:40%,p<0.01);胚胎经过三次反复冻融后形态良好率无显著差别;冷冻2细胞胚移植后的受孕率与仔鼠出生率分别达64%和40%,但均低于新鲜2细胞胚。     

Superovulation Using the Combined Administration of Inhibin Antiserum and Equine Chorionic Gonadotropin Increases the Number of Ovulated Oocytes in C57BL/6 Female Mice

Superovulation is a reproductive technique generally used to produce genetically engineered mice. Superovulation in mice involves the administration of equine chorionic gonadotropin (eCG) to promote follicle growth and then that of human chorionic gonadotropin (hCG) to induce ovulation. Previously, some published studies reported that inhibin antiserum (IAS) increased the number of ovulated oocytes in ddY and wild-derived strains of mice. However, the effect of IAS on the C57BL/6 strain, which is the most widely used inbred strain for the production of genetically engineered mice, has not been investigated. In addition, the combined effect of IAS and eCG (IASe) on the number of ovulated oocytes in superovulation treatment has not been examined. In this study, we examined the effect of IAS and eCG on the number of ovulated oocytes in immature female mice of the C57BL/6 strain in superovulation treatment. Furthermore, we evaluated the quality of obtained oocytes produced by superovulation using IASe by in vitro fertilization (IVF) with sperm from C57BL/6 or genetically engineered mice. The developmental ability of fresh or cryopreserved embryos was examined by embryo transfer. The administration of IAS or eCG had a similar effect on the number of ovulated oocytes in C57BL/6 female mice. The number of ovulated oocytes increased to about 3-fold by the administration of IASe than by the administration of IAS or eCG alone. Oocytes derived from superovulation using IASe normally developed into 2-cell embryos by IVF using sperm from C57BL/6 mice. Fresh or cryopreserved 2-cell embryos produced by IVF between oocytes of C57BL/6 mice and sperm from genetically engineered mice normally developed into live pups following embryo transfer. In summary, a novel technique of superovulation using IASe is extremely useful for producing a great number of oocytes and offspring from genetically engineered mice.     

Involvement of GABA in palate morphogenesis and its relation to diazepam teratogenesis in two mouse strains

Previous studies have indicated that serotonin and acetylcholine stimulate palate shelf reorientation. The present studies were undertaken to determine whether gamma-aminobutyric acid (GABA) functions as an inhibitory neurotransmitter in the palate and whether diazepam mimics GABA to inhibit shelf reorientation and cause cleft palate. First, it was shown that 10(-4) M GABA inhibits palate shelf reorientation in day 14.5 AJ embryos cultured for 2 hours. Anterior palate reorientation stimulated by 10(-5) M serotonin was decreased by GABA; 10(-5) M picrotoxin (GABA antagonist) stimulated anterior shelf reorientation and reversed the effect of GABA. Diazepam (10(-4) M) partially inhibited palate shelf reorientation and that stimulated by 10(-5) M serotonin. Diazepam (400 mg/kg) was administered to AJ mice at day 13.5 of gestation and embryos were cultured at day 14.5. The inhibition produced by diazepam was significantly reduced by 10(-5) M picrotoxin. The teratogenic effect of diazepam was compared with AJ and Swiss-Webster Vancouver (SWV) inbred strains. Diazepam produced greater clefting in SWV mice (57% net) than in the AJ (18% net) when compared to their water- and food-starved controls. The greater sensitivity of the SWV strain than the AJ strain to diazepam, as well as to GABA, was also observed in embryo culture. GABA (10(-5) M) markedly inhibited posterior palate reorientation and reversed the stimulation produced by bethanechol in SWV mice. The inhibitory effects of GABA on the posterior palate were partially reversed by picrotoxin. Furthermore, diazepam inhibited palate reorientation either when administered to the pregnant dam or added in embryo culture.(ABSTRACT TRUNCATED AT 250 WORDS)     

The impaired pregnancy outcome in murine congenital toxoplasmosis is associated with a pro-inflammatory immune response, but not correlated with decidual inducible nitric oxide synthase expression

Congenital toxoplasmosis is associated with adverse pregnancy outcome. Despite the type 1 immune response, C57BL/6 mice are more susceptible than BALB/c mice to Toxoplasma gondii infection. Additionally, successful pregnancy appears to be correlated with type 2 T helper maternal immunity and regulatory T cells. In order to investigate the mechanisms of susceptibility/resistance to congenital toxoplasmosis in mice with different genetic backgrounds and the influence of inducible nitric oxide synthase in pregnancy outcome, groups of C57BL/6, BALB/c and C57BL/6 iNOS(-/-) females were orally infected with T. gondii ME-49 strain on day 1 of pregnancy and were sacrificed on day 8 p.i. and day 19 p.i. The uterus and placenta were evaluated for the foetal resorption rate, parasite load, immunological and histological changes. C57BL/6 mice presented inflammatory foci in the decidua (endometrium) of the uterus at a higher frequency than BALB/c mice on day 8 p.i., and a large number of pregnant C57BL/6 mice presented necrotic implantation sites. The parasite was seldom found in the uterus or placenta of either lineage of mice. Interestingly, there was no observed difference in inducible nitric oxide synthase expression in the uterus and placenta of infected mice. In addition, higher levels of TNF-α were detected in serum samples from C57BL/6 mice compared with BALB/c mice. Accordingly, C57BL/6 mice presented with levels of 90% abortion compared with 50% in BALB/c mice on day 19 p.i. C57BL/6 iNOS(-/-) mice showed low placental parasite counts and high absorption rates, similar to wild type mice. The data suggest that the impaired pregnancy outcome due to T. gondii infection in C57BL/6 mice could be associated with a higher inflammatory response leading to cell apoptosis and necrosis of implantation sites compared with BALB/c mice, and this phenomenon was not due to inducible nitric oxide synthase expression in the decidua.     

A two-locus model for experience-conditioned direction of paw usage in the mouse is suggested by dominant and recessive constitutive paw usage behaviours.

Left-right direction of paw usage in the mouse depends on the genotype and the directional nature of the test. There are two phenotypic classes; in some strains, direction of paw usage is learned or conditioned by the direction of the initial test chamber and the experience of reaching and, in other strains, paw usage is a constitutive behaviour not affected by previous experience. We report the evidence for locus heterogeneity in the cause of constitutive versus experience-conditioned paw usage from a phenotypic analysis of F1 hybrid generations from the experience-conditioned C57BL/6J, C3H/HeHa, and SWV strains and the constitutive CDS/Lay and DBA/2J strains. The F1 hybrids between strains of different phenotypic classes provide evidence of locus heterogeneity. Constitutive paw usage in CDS/Lay is phenotypically dominant to experience-conditioned behaviour in both C57BL/6J and SWV. However, constitutive paw usage in DBA/2J is phenotypically recessive to experience-conditioned behaviour in C57BL/6J and dominant to experience-conditioned behaviour in SWV. Among the experience-conditioned strains, C57BL/6J is highly lateralized but SWV is only weakly lateralized. Our data suggest a model in which C57BL/6J may have a "strong" allele that identifies a functional difference between the constitutive paw usage of CDS/Lay and DBA/2J. DBA/2J may have a loss-of-function mutation at the same locus that is recessive to the strong C57BL/6J allele. SWV may have a "weak" allele and the (SWV x D2)F1 compound heterozygote may be below a threshold for detectability of experience-conditioned behaviour, making the constitutive behaviour of DBA/2J appear to be dominant to the experience-conditioned behaviour of SWV. CDS/Lay may have a dominant allele at a second locus that suppresses experience-conditioned behaviour in all F1 hybrids.     

Analysis of spontaneous early embryonic lethality in mice

The incidence of spontaneously occurring deciduomata is considerably higher in T-stock than in (C3H X C57BL)F1 females. The basis for this difference was studied in vivo, by means of embryo transplantation procedure, and in vitro, by means of short-term embryo culture. Both studies indicate that strain differences in the incidence of spontaneous deciduomata may be largely, if not wholly, accounted for by genetic differences between embryos themselves expressed in terms of the rate of development during the preimplantation period and in the ability to survive the preimplantation and early implantation environment.