Matrix-attachment regions can impart position-independent regulation of a tissue-specific gene in transgenic mice.
Matrix-attachment regions (MARs) may function as domain boundaries and partition chromosomes into independently regulated units. We have tested whether MAR sequences from the chicken lysozyme locus, the so-called A-elements, can confer position-independent regulation to a whey acidic protein (WAP) transgene in mammary tissue of mice. In the absence of MARs, expression of WAP transgenes was observed in 50% of the lines, and regulation during pregnancy, during lactation, and upon hormonal induction did not mimic that of the endogenous WAP gene and varied with the integration site. In contrast, all 11 lines in which WAP transgenes were juxtaposed to MAR elements showed expression. Accurate position-independent hormonal and developmental regulation was seen in four out of the five lines analyzed. These results indicate that MARs can establish independent genetic domains in transgenic mice.
McKnight
R A
RA
Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20982.
Shamay
A
A
Sankaran
L
L
Wall
R J
RJ
Hennighausen
L
L
D000818:Animals; D001665:Binding Sites; D002364:Caseins / Q000235:genetics; D002645:Chickens; D005260:Female; D007774:Lactation; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000235:genetics* / Q000378:metabolism; D009113:Muramidase / Q000235:genetics*; D015345:Oligonucleotide Probes; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015183:Restriction Mapping
D002364:Caseins; D008894:Milk Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; C024471:whey acidic proteins; D009113:Muramidase