TY - JOUR
T1 - Expression of the neurofibromatosis type 1 (NF1) gene during mouse embryonic development
AU - Gutmann, David H.
AU - Cole, Jeffery L.
AU - Collins, Francis S.
N1 - Funding Information:
This work was supported in part by a grant from the NIH (NS-23410) to F.S.C. who was formerly an Investigator with the Howard Hughes Medical Institute. D.H.G. is the recipient of a Career Development Award from the NINDS (NS-01590-02).
PY - 1995/1/1
Y1 - 1995/1/1
N2 - This chapter identifies the von Recklinghausen neurofibromatosis type 1 (NF1) gene by positional cloning; it was found to be a tumor suppressor gene expressed most abundantly in brain. One isoform of NFl (type 2 NFl) contains an additional 21 amino acids inserted into a region of the protein that is involved in the regulation of p21- ras. To study the role of the NF1 gene in mammalian development, the expression of the NFl gene and protein product, neurofibromin, during mouse embryonic development was determined in the experiment discussed in the chapter. NFl mRNA and neurofibromin expression was detectable by Northern and Western analysis, respectively, after day 10 of murine embryogenesis and remained elevated throughout development. Type 2 NFl mRNA expression predominated before day 10, after which e type 1 NF1 mRNA was the predominant isoform detected. The protein expression of the type 2 isoform was similar to overall neurofibromin expression by Western blot analysis, with greatest expression in adult brain. Despite a similar tissue distribution pattern, type 2 neurofibromin was not found to be associated with brain cytoplasmic microtubules. These experiments suggest that the switch from type 2 to type 1 eurofibromin isoform predominance during embryogenesis may have significant functional consequences.
AB - This chapter identifies the von Recklinghausen neurofibromatosis type 1 (NF1) gene by positional cloning; it was found to be a tumor suppressor gene expressed most abundantly in brain. One isoform of NFl (type 2 NFl) contains an additional 21 amino acids inserted into a region of the protein that is involved in the regulation of p21- ras. To study the role of the NF1 gene in mammalian development, the expression of the NFl gene and protein product, neurofibromin, during mouse embryonic development was determined in the experiment discussed in the chapter. NFl mRNA and neurofibromin expression was detectable by Northern and Western analysis, respectively, after day 10 of murine embryogenesis and remained elevated throughout development. Type 2 NFl mRNA expression predominated before day 10, after which e type 1 NF1 mRNA was the predominant isoform detected. The protein expression of the type 2 isoform was similar to overall neurofibromin expression by Western blot analysis, with greatest expression in adult brain. Despite a similar tissue distribution pattern, type 2 neurofibromin was not found to be associated with brain cytoplasmic microtubules. These experiments suggest that the switch from type 2 to type 1 eurofibromin isoform predominance during embryogenesis may have significant functional consequences.
UR - http://www.scopus.com/inward/record.url?scp=0029097086&partnerID=8YFLogxK
U2 - 10.1016/S0079-6123(08)63311-7
DO - 10.1016/S0079-6123(08)63311-7
M3 - Article
C2 - 7568895
AN - SCOPUS:0029097086
SN - 0079-6123
VL - 105
SP - 327
EP - 335
JO - Progress in Brain Research
JF - Progress in Brain Research
IS - C
ER -