Wild-type Dams Research Articles

Growth Retardation, Duodenal Lesions, and Aberrant Ileum Architecture in Triple Null Mice Lacking EGF, Amphiregulin, and TGF-α

Background & Aims: Mice lacking epidermal growth factor (EGF), transforming growth factor α, and amphiregulin were used to identify roles for these EGF receptor (EGF-R) ligands in gastrointestinal development and mucosal integrity. Methods: Gastrointestinal tract development was examined in knockout mice and correlated with expression of EGF-R protein and EGF family members throughout the gut. Crossfostering experiments addressed roles of maternal- and neonatal-derived ligands in pup growth and intestinal development. Cysteamine-induced ulceration in EGF −/− mice was used to examine its role in mucosal cytoprotection. Results: Neonatal mice lacking all 3 ligands were growth retarded, even when reared by wild-type dams; conversely, lack of maternal ligands transiently impaired wild-type pup growth. Triple null neonates displayed spontaneous duodenal lesions, and ileal villi were truncated and fragile with reduced cellular proliferation in the crypts. However, maturation of digestive enzymes was unaffected. Adult EGF −/− mice displayed more severe lesions in response to cysteamine treatment compared with wild-type counterparts, although triple null mice were not more susceptible to dextran sulfate sodium-induced colitis, suggesting a differential role for these ligands in the injury response. Conclusions: EGF-R ligands are required for development and mucosal maintenance in mouse small intestine. Both maternal and neonatal sources of growth factors are required for optimal pup growth.

Maternal and pup genotype contribution to growth in wild-type and tau mutant Syrian hamsters.

The single gene mutation tau in the Syrian hamster-apart from its effect on the circadian organization of locomotor activity--has a pronounced influence on body weight. In this study we investigate the impact of maternal and pup genotypes at the tau-locus on the growth rate of pups. Homozygous tau mutant hamsters (circadian period of 20 hours) had lower growth rates and adult body weights than wild-type hamsters, whereas heterozygous tau mutants (circadian period of 22 hours) were intermediate. In addition, heterozygous pups from heterozygous dams grew heavier than those from wild-type and homozygous dams. The effect of maternal genotype was further evaluated in a cross-foster design, where wild-type and homozygous mutant pups were fostered at birth to either wild-type or homozygous mutant dams. At all ages, the maternal tau genotype had a negative effect on body weight, whereas the pup tau genotype had a positive effect during the preweaning period and a negative effect afterward.

Oxytocin and milk removal are required for post-partum mammary-gland development.

The oxytocin (OT)-neurophysin preprohormone is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. OT is cleaved from its precursor, transported from the magnocellular neurons to the posterior pituitary and secreted during labour and upon the suckling stimulus of pups. OT induces the contraction of myoepithelial cells surrounding the mammary alveoli, which leads to the ejection of milk. Mice deficient in OT are unable to nurse their young. Administration of OT enabled OT-deficient dams to nurse. We now show that OT and milk removal are also required for post-partum alveolar proliferation and mammary-gland function. Alveolar density and mammary epithelial-cell differentiation at parturition was similar in wild-type and OT-deficient dams. However, within 12 h after parturition approx. 2% of the alveolar cells in wild-type dams incorporated DNA and proliferated, but virtually no proliferation was detected in OT-deficient dams. Continuous suckling of pups led to the expansion of lobulo-alveolar units in wild-type but not in OT-deficient dams. Despite suckling and the presence of systemic lactogenic hormones, mammary tissue in OT-deficient dams partially involuted. Our studies demonstrate that post-partum alveolar proliferation requires not only systemic lactogenic hormones, such as prolactin, but also the presence of OT in conjunction with continued milk removal.