Nu skulle man tro, at historien om patienteme
med Imerslund-Gräsbecks syndrom var afsluttet.
Men dette er ikke tilf::eldet. Patienter uden for
Finland synes ikke at have FM1 eller FM2 muta–
tionerne, og der kendes nu Imerslund-Gräsbeck
patienter med normalt cubilingen. Disse patienter
formodes derimod at have defekter i proteiner,
der er vigtige for cubilins funktion. For eksempel
kunne proteiner involveret i processeringen af
cubilin v::ere defekte, som det er tilf::eldet for en
gruppe af hunde med et sygdomsbillede, der er
identisk med Imerslund-Gräsbecks syndrom
10
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*Mette Madsen har indtil for nylig publiceret
under navnet
Mette Kristiansen.
Referencer:
l. Moestrup SK, Kozyraki R, Kristiansen M,
Kaysen JH, Rasmussen
HH,
Brault D, Pontil–
lon F, Goda FO, Christensen El, Hamrnond
TG, Verroust PJ: The intrinsic factor-vitamin
B
l2
receptor and target of teratogenic antibo–
dies is a megalin-binding peripheral membrane
protein with homology to developmental
proteins. J.Biol.Chem. 273: 5235-5242, 1998
2. Kozyraki R, Kristiansen M, Silahtaroglu A,
Hansen C, Jacobsen C, Tommerup N, Verroust
PJ, Moestrup SK: The human intrinsic factor–
vitamin B
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receptor, cubilin: molecular cha–
racterization and chromosomal mapping of
the gene to lOp within the autosomal recessive
megaloblastic anemia (MGA1) region. Blood
91 : 3593-3600, 1998
3. Moestrup SK, Verroust PJ: Megalin-and cubi–
lin-mediated endocytosis of protein-bound
vitamins, lipids, and hormorres in polarized
epithelia. Annu Rev Nutr 21: 407-428, 2001
4. Hammad SM, Barth JL, Knaak C, Argraves
WS: Megalin acts in concert with cubilin to
mediate endocytosis of high density lipopro–
teins. J.Biol.Chem. 275: 12003-12008, 2000
5. Kozyraki R, Fyfe J, Verroust PJ, Jacobsen C,
Dautry-Varsat A, Gburek J, Willnow TE, Chris–
tensen El, Moestrup SK: Megalin-dependent
cubilin-mediated endocytosis is a major path–
way for the apical uptake of transterrin in
polarized epithelia. Proc.Natl.Acad.Sci.U.S.A
98: 12491-12496,2001
Klinisk Kjemi i Norden 4, 2001
6. Kristiansen M, Kozyraki R, Jacobsen C, Nex!ZI
E, Verroust PJ, Moestrup SK: Molecular dis–
seetian of the intrinsic factor-vitamin B
12
receptor, cubilin, discloses regions important
for membrane association and ligand binding.
J.Biol.Chem. 274: 20540-20544, 1999
7. Kristiansen M, Aminoff M, Jacobsen C, de la
CA, Krahe R, Verroust PJ, Moestrup SK:
Cubilin Pl297L mutation associated with
hereditary megaloblastic anemia l eauses
impaired recognition of intrinsic factor-vita–
min B
12
by cubilin. Blood 96: 405-409, 2000
8. Aminoff M, Tahvanainen E, Grasbeck R,
Weissenbach J, Broch H, de la CA: Selective
intestina! malabsorption of vitamin B
12
dis–
plays recessive mendehan inheritance: assign–
ment of a locus to chromosome l Oby linkage.
Am.J.Hum.Genet. 57: 824-831, 1995
9. Aminoff M, Carter JE, Chadwick RB, John–
son C, Grasbeck R, Abdelaal MA, Broch H,
Jenner LB, Verroust PJ, Moestrup SK, de la
Chapelle A, Krahe R: Mutations in CUBN,
encoding the intrinsic factor-vitamin B
l2
receptor, cubilin, cause hereditary megalob–
lastic anaemia
l.
Nat Genet 21: 309-313, 1999
10. Fyfe JC, Giger U, Hall CA, Jezyk PF, Klumpp
SA, Levine JS , Fatterson DF: Inherited selec–
tive intestina) cobalamin malabsorption and
cobalamin deficiency in dogs . Pediatr.Res. 29:
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11. Fyfe JC, Ramanujam KS , Ramaswamy K,
Fatterson DF, Seetharam B: Defective brush–
border expression of intrinsic factor-cabala–
min receptor in canine inherited intestina!
cobalamin malabsorption. J.Biol.Chem. 266:
4489-4494, 1991
12. Xu D, Kozyraki R, Newman TC, Fyfe JC:
Genetic Evidence of an Accessory Activity
Required Specifically for Cubilin Brush-Bor–
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min Absorption. Blood 94: 3604-3606, 1999
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