Ethanol teratogenesis in five inbred strains of mice.

BACKGROUND Previous studies have demonstrated individual differences in susceptibility to the detrimental effects of prenatal ethanol exposure. Many factors, including genetic differences, have been shown to play a role in susceptibility and resistance, but few studies have investigated the range of genetic variation in rodent models. METHODS We examined ethanol teratogenesis in 5 inbred strains of mice: C57BL/6J (B6), Inbred Short-Sleep, C3H/Ibg, A/Ibg, and 129S6/SvEvTac (129). Pregnant dams were intubated with either 5.8 g/kg ethanol (E) or an isocaloric amount of maltose-dextrin (MD) on day 9 of pregnancy. Dams were sacrificed on day 18 and fetuses were weighed, sexed, and examined for gross morphological malformations. Every other fetus within a litter was then either placed in Bouin's fixative for subsequent soft-tissue analyses or eviscerated and placed in ethanol for subsequent skeletal analyses. RESULTS B6 mice exposed to ethanol in utero had fetal weight deficits and digit, kidney, brain ventricle, and vertebral malformations. In contrast, 129 mice showed no teratogenesis. The remaining strains showed varying degrees of teratogenesis. CONCLUSIONS Differences among inbred strains demonstrate genetic variation in the teratogenic effects of ethanol. Identifying susceptible and resistant strains allows future studies to elucidate the genetic architecture underlying prenatal alcohol phenotypes.

[1]  L. Wickstrom,et al.  SALMONELLAS IN MEAT. , 1964, Lancet.

[2]  J. Wilson.  Methods for administering agents and detecting malformations in experimental animals , 1965 .

[3]  A. Streissguth,et al.  Pattern of Malformation in Offspring of Chronic Alcoholic Mothers , 1995, Alcohol health and research world.

[4]  David W. Smith,et al.  Recognition of the fetal alcohol syndrome in early infancy. , 1973, Lancet.

[5]  R. Palmer,et al.  Congenital malformations in offspring of a chronic alcoholic mother. , 1974, Pediatrics.

[6]  K. Christoffel,et al.  Fetal alcohol syndrome in dizygotic twins. , 1975, The Journal of pediatrics.

[7]  D. Walker,et al.  Ethanol-induced malformations in mice. , 1977, Alcoholism, clinical and experimental research.

[8]  R. Lowry.  The Klippel-Feil anomalad as part of the fetal alcohol syndrome. , 1977, Teratology.

[9]  M. Debeukelaer,et al.  Renal anomalies in the fetal alcohol syndrome. , 1977, The Journal of pediatrics.

[10]  G. Chernoff.  The fetal alcohol syndrome in mice: an animal model. , 1977, Teratology.

[11]  S. M. Sumi,et al.  Brain malformations related to prenatal exposure to ethanol. , 1978, The Journal of pediatrics.

[12]  K. Jones,et al.  The fetal alcohol syndrome. , 1975, The Lamp.

[13]  L. Neidengard,et al.  Klippel-Feil malformation complex in fetal alcohol syndrome. , 1978, American journal of diseases of children.

[14]  Q. Qazi,et al.  Renal anomalies in fetal alcohol syndrome. , 1979, Pediatrics.

[15]  G. Chernoff.  The fetal alcohol syndrome in mice: maternal variables. , 1980, Teratology.

[16]  I. Damjanov,et al.  The differential transplacental effects of ethanol in four mouse strains. , 1980 .

[17]  P. Tam,et al.  The control of somitogenesis in mouse embryos. , 1981, Journal of embryology and experimental morphology.

[18]  van Rensburg Lj.  Major skeletal defects in the fetal alcohol syndrome. A case report. , 1981 .

[19]  D. E. Newman,et al.  Intrinsic defects in the fetal alcohol syndrome: studies on 76 cases from British Columbia and the Yukon Territory. , 1981, Neurobehavioral toxicology and teratology.

[20]  S. Tredwell,et al.  Cervical Spine Anomalies in Fetal Alcohol Syndrome , 1982, Spine.

[21]  W. Webster,et al.  Some teratogenic properties of ethanol and acetaldehyde in C57BL/6J mice: implications for the study of the fetal alcohol syndrome. , 1983, Teratology.

[22]  P. Wainwright,et al.  Moderate prenatal ethanol exposure interacts with strain in affecting brain development in BALB c and , 1985, Experimental Neurology.

[23]  I. Chasnoff.  Fetal alcohol syndrome in twin pregnancy. , 1985, Acta geneticae medicae et gemellologiae.

[24]  R. Pauli,et al.  Major limb malformations following intrauterine exposure to ethanol: two additional cases and literature review. , 1986, Teratology.

[25]  J. West,et al.  Microencephaly and hyperactivity in adult rats can be induced by neonatal exposure to high blood alcohol concentrations , 1987, Experimental Neurology.

[26]  P. Wainwright,et al.  Heredity and alcohol-induced brain anomalies: Effects of alcohol on anomalous prenatal development of the corpus callosum and anterior commissure in BALB c , 1987, Experimental Neurology.

[27]  R. Anton,et al.  Role of alcohol-induced hypothermia in mediating the teratogenic effects of alcohol in C57BL/6J mice. , 1988, Alcoholism, clinical and experimental research.

[28]  B. Dudek,et al.  Ethanol teratogenesis in mice selected for differences in alcohol sensitivity. , 1988, Alcohol.

[29]  T. Kajii,et al.  Severe skeletal dysplasias following intrauterine exposure to ethanol. , 1988, Teratology.

[30]  B. Dudek,et al.  Ethanol Teratogenesis in Selectively Bred Long‐Sleep and Short‐Sleep Mice: A Comparison to Inbred C57BL/6J Mice , 1989 .

[31]  W. Scott,et al.  Ethanol-induced limb defects in mice: effect of strain and Ro15-4513. , 1990, Teratology.

[32]  Alcohol-related birth defects in long- and short-sleep mice: postnatal litter mortality. , 1990, Alcohol.

[33]  A. Streissguth,et al.  Prenatal alcohol exposure: comparability of effects in humans and animal models. , 1990, Neurotoxicology and teratology.

[34]  D. Gilliam,et al.  Maternal genetic effects on ethanol teratogenesis and dominance of relative embryonic resistance to malformations. , 1990, Alcoholism, clinical and experimental research.

[35]  T. Persaud,et al.  Prenatal influence of alcohol following a single exposure in two inbred strains of mice. , 1992, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[36]  U. Froster,et al.  Congenital defects of the limbs and alcohol exposure in pregnancy: data from a population based study. , 1992, American journal of medical genetics.

[37]  A. Streissguth,et al.  Fetal alcohol syndrome in twins of alcoholic mothers: concordance of diagnosis and IQ. , 1993, American journal of medical genetics.

[38]  I. Chahoud,et al.  Time-dependent differences in the development of somites of four different mouse strains. , 1993, Teratogenesis, carcinogenesis, and mutagenesis.

[39]  R. Riikonen.  Difference in susceptibility to teratogenic effects of alcohol in discordant twins exposed to alcohol during the second half of gestation. , 1994, Pediatric neurology.

[40]  K. Jones,et al.  Incidence of renal anomalies in children prenatally exposed to ethanol. , 1994, Pediatrics.

[41]  E. Abel.  An update on incidence of FAS: FAS is not an equal opportunity birth defect. , 1995, Neurotoxicology and teratology.

[42]  J. Hannigan,et al.  Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences. , 1995, Neurotoxicology and teratology.

[43]  D. Gilliam,et al.  Dose-related growth deficits in LS but not SS mice prenatally exposed to alcohol. , 1996, Alcohol.

[44]  D. Gilliam,et al.  Ethanol teratogenesis in the C57BL/6J, DBA/2J, and A/J inbred mouse strains. , 1997, Alcohol.

[45]  Ting-kai Li,et al.  Alcohol dehydrogenase-2*3 allele protects against alcohol-related birth defects among African Americans. , 1997, The Journal of pharmacology and experimental therapeutics.

[46]  Y. Bobryshev,et al.  Disorders of brain development in the progeny of mothers who used alcohol during pregnancy. , 1997, Early human development.

[47]  F L Bookstein,et al.  Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. , 1997, Teratology.

[48]  D. Gilliam,et al.  Effects of acute prenatal ethanol administration in a reciprocal cross of C57BL/6J and short-sleep mice: maternal effects and nonmaternal factors. , 1997, Alcoholism, clinical and experimental research.

[49]  J. Crabbe,et al.  Identifying genes for alcohol and drug sensitivity: recent progress and future directions , 1999, Trends in Neurosciences.

[50]  D. Gilliam,et al.  Cytoplasmic Factors Do Not Contribute to a Maternal Effect on Ethanol Teratogenesis , 1999, Behavior genetics.

[51]  P. May,et al.  Estimating the prevalence of fetal alcohol syndrome. A summary. , 2001 .

[52]  C. Coles.  Fetal Alcohol Exposure and Attention: Moving Beyond ADHD , 2001, Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism.

[53]  Ting-kai Li,et al.  Alcohol dehydrogenase-2*2 allele is associated with decreased prevalence of fetal alcohol syndrome in the mixed-ancestry population of the Western Cape Province, South Africa. , 2001, Alcoholism, clinical and experimental research.

[54]  P. Tam,et al.  7 – Somitogenesis: Segmentation of the Paraxial Mesoderm and the Delineation of Tissue Compartments , 2002 .

[55]  J. Stoler,et al.  Alcohol dehydrogenase 2 genotypes, maternal alcohol use, and infant outcome. , 2002, The Journal of pediatrics.

[56]  G. Leonardson,et al.  Risk factors for alcohol use during pregnancy in a multistate area. , 2003, Neurotoxicology and teratology.

[57]  Gideon Koren,et al.  Fetal Alcohol Spectrum Disorder , 2010 .

[58]  R. Sokol,et al.  Fetal alcohol spectrum disorder. , 2003, JAMA.

[59]  D. G. McCarver,et al.  Alcohol dehydrogenase 2*3 affects alterations in offspring facial morphology associated with maternal ethanol intake in pregnancy. , 2004, Alcoholism, clinical and experimental research.

[60]  J. Borzelleca,et al.  Characteristics of children who have full or incomplete fetal alcohol syndrome. , 2004, The Journal of pediatrics.

[61]  F. Assadi.  Renal tubular dysfunction in fetal alcohol syndrome , 2004, Pediatric Nephrology.

[62]  C. Downing,et al.  Murine Models of Alcoholism , 2005 .

[63]  M. Schilgen,et al.  Klippel-Feil anomaly combined with fetal alcohol syndrome , 2005, European Spine Journal.

[64]  J. Treadwell.  Integrative strategies to identify candidate genes in rodent models of human alcoholism. , 2006, Genome.

[65]  C. Downing,et al.  Mouse genetic models in alcohol research. , 2006, Trends in genetics : TIG.

[66]  E. S. Hunter,et al.  Perturbation of retinoic acid (RA)-mediated limb development suggests a role for diminished RA signaling in the teratogenesis of ethanol. , 2007, Birth defects research. Part A, Clinical and molecular teratology.

[67]  Ronald E. Goldstein,et al.  Principles and techniques , 2009 .