Summary
Citation
Burdon, T., Wall, R.J., Shamay, A., Smith, G.H. and Hennighausen, L. (1991). Overexpression of an endogenous milk protein gene in transgenic mice is associated with impaired mammary development and a milchlos phenotype. Mech. of Development 36, 67-74.
Burdon, T., Wall, R.J., Shamay, A., Smith, G.H. and Hennighausen, L. (1991). Overexpression of an endogenous milk protein gene in transgenic mice is associated with impaired mammary development and a milchlos phenotype. Mech. of Development 36, 67-74.
Background
While analyzing mice carrying a mouse WAP transgene in 1990, Tom Burdon observed that females from two lines could not nurse their litters. Since these mice were unable to produce milk their phenotype was named milchlos. A similar phenotype was observed in transgenic pigs expressing the same mouse WAP transgene, and in mice carrying a MMTV-LTR/WAP transgene.
Transgene
A 7 kb mouse WAP gene (GR strain) containing 2.4 kb of promoter and 1.6 kb of 3' flanking sequence.
mouse strain
The transgene was introduced into a C57/B5 x SJL background.
Mammary development
Gene expression
While high levels of endogenous WAP RNA are only found around day 16 of pregnancy the WAP transgene is expressed already at day 10 of pregnancy. Expression of the milk protein genes, WDNM1, b-casein, WAP and a-lactalbumin is detected. However, expression of the a-lactalbumin gene is highly deregulated. a-lactalbumin RNA is being found precociously around day 10 of pregnancy and its concentration at parturition is only 10% of that found in
non-transgenic littermates (Robinson et al., 1995).
Mechanistic implications
Ducts
Overall ductal outgrowth during puberty and pregnancy appears to be normal.
Alveoli
Alveolar development is impaired and in none of the mice the fat pad is completely filled during pregnancy. There is variation in alveolar outgrowth; in some
of the mice at parturition, the alveolar structures are almost absent, and in others they mimic an 18 day pregnant gland.
key words
whey acidic protein, WAP, transgenic, milk, agalactia, milchlos, mammary development, lactalbumin, WDNM1
Submitted by : Lothar Henninghausen
Contact: mammary@nih.gov