The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in newborn mice.
In mice, the recessive mutation hairless (hr) controls the cutaneous response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD's systemic toxicity is unclear. To clarify this, we compared the effects of lactational TCDD exposure on standardized litters of newborn HRS/J mice homozygous for either hr or + that were fostered by haired dams exposed to 0, 6, 8 or 12 micrograms TCDD/kg body weight on postnatal day 0. At 12 micrograms/kg, TCDD was lethal to both haired and hairless pups. At the lower doses (6 and 8 micrograms/kg) the survival of hr/hr pups was significantly lower than +/+ pups. Affected pups succumbed following a 1 to 2-day period of cachexia and wasting. As has been reported for other mouse strains, TCDD exposure impacted on their neonatal development and lessened the time to eye opening for both haired and hairless pups. However, the hairless animals were affected at lower doses than were the haired. The results of this study document that the hr/hr genotype does influence the systemic toxicity of TCDD in mice.
Connor
M J
MJ
Department of Medicine, UCLA School of Medicine 90024.
Puhvel
S M
SM
Sakamoto
M
M
Nanthur
J
J
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics*; D001835:Body Weight / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000187:drug effects; D051379:Mice; D008812:Mice, Hairless / Q000235:genetics; D009154:Mutation; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins