Butyrophilin, subfamily 1, member A1 explained

Butyrophilin subfamily 1 member A1 is a protein that in humans is encoded by the BTN1A1 gene.^{[1] [2] [3]}

Butyrophilin (BTN) is the major protein associated with fat droplets in the milk. It is a member of the immunoglobulin superfamily. It may have a cell surface receptor function. The human butyrophilin gene is localized in the major histocompatibility complex (MHC) class I region of 6p and may have arisen relatively recently in evolution by the shuffling of exons between 2 ancestral gene families^[3]

Function

Btn1a1 regulates the amount of lipids and size of droplets expressed in milk. When the gene is compromised in laboratory mice, approximately half the pups died within the first 20 days and the remainder were significantly under-weight.^[4]

Link to multiple sclerosis

Butyrophilin has been presented as a potential antigen which may be similar enough to myelin oligodendrocyte glycoprotein (MOG) to spur the immune system to attack myelin in a process known as molecular or epitopic mimicry. This suggests that ingestion of butyrophilin in dairy products from cows and goats may be a potential trigger for multiple sclerosis. Independent studies by a group in Germany have reached similar conclusions.^{[5] [6]}

The German group have used heavy doses of butyrophilin on mice with an experimental model for multiple sclerosis called EAE. They have found that this strategy, called immune tolerance, reduces the effects of the disease.

Further reading

• Mather IH, Jack LJ . A review of the molecular and cellular biology of butyrophilin, the major protein of bovine milk fat globule membrane. . J. Dairy Sci. . 76 . 12 . 3832–50 . 1994 . 8132890 . 10.3168/jds.s0022-0302(93)77726-7. free .
• Heid HW, Winter S, Bruder G . Butyrophilin, an apical plasma membrane-associated glycoprotein characteristic of lactating mammary glands of diverse species. . Biochim. Biophys. Acta . 728 . 2 . 228–38 . 1983 . 6830779 . 10.1016/0005-2736(83)90476-5. etal.
• Sato T, Takio K, Kobata A . Site-specific glycosylation of bovine butyrophilin. . J. Biochem. . 117 . 1 . 147–57 . 1995 . 7775382 . 10.1093/oxfordjournals.jbchem.a124702. etal.
• Taylor MR, Peterson JA, Ceriani RL, Couto JR . Cloning and sequence analysis of human butyrophilin reveals a potential receptor function. . Biochim. Biophys. Acta . 1306 . 1 . 1–4 . 1996 . 8611614 . 10.1016/0167-4781(19)60000-x.
• Cavaletto M, Giuffrida MG, Giunta C . Multiple forms of lactadherin (breast antigen BA46) and butyrophilin are secreted into human milk as major components of milk fat globule membrane. . J. Dairy Res. . 66 . 2 . 295–301 . 1999 . 10376248 . 10.1017/s0022029999003507. 29228427 . etal.
• Shibui A, Tsunoda T, Seki N . Cloning, expression analysis, and chromosomal localization of a novel butyrophilin-like receptor. . J. Hum. Genet. . 44 . 4 . 249–52 . 1999 . 10429365 . 10.1007/s100380050153. etal. free .
• Rhodes DA, Stammers M, Malcherek G . The cluster of BTN genes in the extended major histocompatibility complex. . Genomics . 71 . 3 . 351–62 . 2001 . 11170752 . 10.1006/geno.2000.6406 . etal.
• McManaman JL, Palmer CA, Wright RM, Neville MC . Functional regulation of xanthine oxidoreductase expression and localization in the mouse mammary gland: evidence of a role in lipid secretion. . J. Physiol. . 545 . Pt 2 . 567–79 . 2003 . 12456835 . 10.1113/jphysiol.2002.027185. 2290700.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . etal. free .
• Mungall AJ, Palmer SA, Sims SK . The DNA sequence and analysis of human chromosome 6. . Nature . 425 . 6960 . 805–11 . 2003 . 14574404 . 10.1038/nature02055 . 2003Natur.425..805M . etal. free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928. etal.
• Woo JS, Imm JH, Min CK . Structural and functional insights into the B30.2/SPRY domain. . EMBO J. . 25 . 6 . 1353–63 . 2006 . 16498413 . 10.1038/sj.emboj.7600994 . 1422157. etal.

Notes and References

1. Vernet C, Boretto J, Mattei MG, Takahashi M, Jack LJ, Mather IH, Rouquier S, Pontarotti P . Evolutionary study of multigenic families mapping close to the human MHC class I region . J Mol Evol . 37 . 6 . 600–12 . Mar 1994 . 8114113 . 10.1007/bf00182746. 19054302 .
2. Tazi-Ahnini R, Henry J, Offer C, Bouissou-Bouchouata C, Mather IH, Pontarotti P . Cloning, localization, and structure of new members of the butyrophilin gene family in the juxta-telomeric region of the major histocompatibility complex . Immunogenetics . 47 . 1 . 55–63 . Jan 1998 . 9382921 . 10.1007/s002510050326. 1873778 .
3. Web site: Entrez Gene: BTN1A1 butyrophilin, subfamily 1, member A1.
4. Expression of butyrophilin (Btn1a1) in lactating mammary gland is essential for the regulated secretion of milk–lipid droplets. Sherry L. Ogg. Anne K. Weldon . Lorraine Dobbie . Andrew J. H. Smith . Ian H. Mather . Proceedings of the National Academy of Sciences. 6 July 2004. 101. 27. 10084–10089. 10.1073/pnas.0402930101. 15226505. 454168. 2004PNAS..10110084O . free.
5. Stefferl A, Schubart A, Storch M, Amini A, Mather I, Lassmann H, Linington C . Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis . J. Immunol. . 165 . 5 . 2859–65 . September 2000 . 10946319 . 10.4049/jimmunol.165.5.2859. free .
6. Guggenmos J, Schubart AS, Ogg S, Andersson M, Olsson T, Mather IH, Linington C . Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis . J. Immunol. . 172 . 1 . 661–8 . January 2004 . 14688379 . 10.4049/jimmunol.172.1.661. free .