Exogenous Sonic hedgehog protein does not rescue cultured intestine from atresia formation.

Background: The mechanism of intestinal atresia formation remains undefined. Atresia in fibroblast growth factor receptor 2IIIb (Fgfr2IIIb(-/-)) mutant mouse embryos is preceded by endodermal apoptosis and involution of the surrounding mesoderm. We have observed that involution of the atretic segment is preceded by the downregulation of Sonic hedgehog (SHH) in the endoderm, which is a critical organizer of the intestinal mesoderm.

Utility and limits of Hprt-Cre technology in generating mutant mouse embryos.

Background: Hprt-Cre doubles the prevalence of homozygous null embryos per litter versus heterozygous breedings without decreasing litter size. Resulting mutant embryos are genotypically and phenotypically equivalent between strategies. We set out to confirm the effectiveness of this approach with other alleles and hypothesized that it would increase efficiency in generating compound mutants.

Haploinsufficiency of retinaldehyde dehydrogenase 2 decreases the severity and incidence of duodenal atresia in the fibroblast growth factor receptor 2IIIb-/- mouse model.

Background: Homozygous null mutation of the fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) gene in mice results in 42% of embryos developing duodenal atresias. Retinaldehyde dehydrogenase 2 (Raldh2, a gene critical for the generation of retinoic acid) is expressed in the mouse duodenum during the temporal window when duodenal atresias form. Raldh2 is critical for the normal development of the pancreatoduodenal region; therefore, we were interested in the effect of a Raldh2 mutation on duodenal atresia formation.

Formation of duodenal atresias in fibroblast growth factor receptor 2IIIb-/- mouse embryos occurs in the absence of an endodermal plug.

Purpose: Duodenal atresia in humans has been hypothesized to arise from a failure of the duodenal lumen to recanalize after formation of an endodermal plug. Recently, mutations in the fibroblast growth factor receptor 2 gene (Fgfr2IIIb) have been shown to cause atretic defects of the duodenum in mice. However, work in rats suggests that murine species do not form an endodermal plug during normal duodenal development.

Formation of intestinal atresias in the Fgfr2IIIb-/- mice is not associated with defects in notochord development or alterations in Shh expression.

Purpose: The etiology of intestinal atresia remains elusive but has been ascribed to a number of possible events including in utero vascular accidents, failure of recanalization of the intestinal lumen, and mechanical compression. Another such event that has been postulated to be a cause in atresia formation is disruption in notochord development. This hypothesis arose from clinical observations of notochord abnormalities in patients with intestinal atresias as well as abnormal notochord development observed in a pharmacologic animal model of intestinal atresia.

A more efficient method to generate null mutants using Hprt-Cre with floxed alleles.

Purpose: The generation of nonviable homozygous null mouse embryos from heterozygote null/+ breedings can be highly resource consuming, with only 25% of the embryos in the litter being null mutants. We hypothesized that (1) we could double the number of homozygous null mouse embryos in a litter without reducing litter size using Hypoxanthine-guanine phosphoribosyltransferase-Cre (Hprt)-Cre (which is active in the female germ line at the time of fertilization), and (2) these homozygous null mutants would be identical to mutants generated through traditional null/+ breedings.

Methods: To test this hypothesis, we used a conditional allele Fgfr2IIIb(flox).

Conditional mutation of fibroblast growth factor receptors 1 and 2 results in an omphalocele in mice associated with disruptions in ventral body wall muscle formation.

Background/purpose: We observed that fibroblast growth factor receptors 1 and 2 (Fgfr1, Fgfr2) are expressed during abdominal wall development in mice and hypothesized that conditional mutation of these genes would result in abdominal wall defects.

Methods: Section in situ hybridizations were performed for Fgfr1 and Fgfr2 on wild-type embryos at embryonic day (E) 11.5 and E13.

Humans, mice, and mechanisms of intestinal atresias: a window into understanding early intestinal development.

Introduction: Intestinal atresias have long been hypothesized to result from either failure of recanalization of the intestinal lumen or in utero vascular accidents. Recent work in animal models is now calling for a reassessment of these widely held paradigms.

Purpose: In this review, we will examine the data that led to the original hypotheses and then evaluate more recent work challenging these hypotheses.

Intersexuality and the cricket frog decline: historic and geographic trends.

Exposure to anthropogenic endocrine disruptors has been listed as one of several potential causes of amphibian declines in recent years. We examined gonads of 814 cricket frogs (Acris crepitans) collected in Illinois and deposited in museum collections to elucidate relationships between the decline of this species in Illinois and the spatial and temporal distribution of individuals with intersex gonads. Compared with the preorganochlorine era studied (1852-1929), the percentage of intersex cricket frogs increased during the period of industrial growth and initial uses of polychlorinated biphenyls (PCBs) (1930-1945), was highest during the greatest manufacture and use of p,p-dichlorodiphenyltrichloroethane (DDT) and PCBs (1946-1959), began declining with the increase in public concern and environmental regulations that reduced and then prevented sales of DDT in the United States (1960-1979), and continued to decline through the period of gradual reductions in environmental residues of organochlorine pesticides and PCBs in the midwestern United States (1980-2001).

Informed lay preferences for delivery of racially varied pharmacogenomics.

Objectives: To understand public perceptions and opinions of three options for prescribing medicine: individualized genetic testing, race-based prescription, and traditional prescription.

Methods: Focus groups in urban, suburban, and rural communities over-sampled for minority groups conducted from February through April, 2001 in Georgia.

Results: Group members (N = 102) identified individualized genetic testing as providing the best quality of care (60% of talk turns; 75% in postdiscussion anonymous survey), but stipulated the need for protection from the invasion of privacy, discrimination, and prohibitive cost.