User:Rockpocket/Git2
ARF GTPase-activating protein GIT2 is an enzyme that in humans is encoded by the GIT2 gene.[1][2][3]
This gene encodes a member of the GIT protein family. GIT proteins interact with G protein-coupled receptor kinases and possess ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) activity. This gene undergoes extensive alternative splicing; although ten transcript variants have been described, the full length sequence has been determined for only four variants. The various isoforms have functional differences, with respect to ARF GAP activity and to G protein-coupled receptor kinase 2 binding.[3]
Animal models
[edit]Model organisms have been used in the study of GIT2 function. A conditional knockout mouse line, called Git2Gt(XG510)Byg,[4] was analysed at the Wellcome Trust Sanger Institute as part of a large scale phenotypic screen.[5][6][7][8]
| Characteristic | Abnormal |
|---|---|
| Homozygote viability | No |
| Fertility | No |
| Body weight | No |
| Hair follicle cycling | No |
| Anxiety | No |
| Modified SHIRPA | No |
| Grip strength | No |
| Heat response | Yes[9] |
| Dysmorphology | No |
| Indirect calorimetry | No |
| Glucose tolerance test | No |
| Auditory brainstem response | No |
| DEXA | No |
| Radiography | No |
| Body temperature | No |
| Eye morphology | No |
| Heart weight | No |
| Heart histology | No |
| Histology | No |
| Clinical chemistry | Yes[10] |
| Plasma immunoglobulins | No |
| Haematology | Yes[11] |
| Peripheral blood lymphocytes | No |
| Micronucleus test (naive) | No |
| Micronucleus test (irradiated) | No |
| Skin immunofluorescence | No |
| Brain histology | Yes[8] |
| All tests and analysis from [7][8] | |
Mice lacking Git2 had no significant defects in viability or fertility,[12][13] so further tests were carried out and four significant phenotypes were reported:[6][8]
- Mutant mice had differences in their clinical blood chemistry compared to wildtype control mice.
- Mutant male mice had a decrease in white blood cell count.
- An increased thickness in hippocampus was observed.
- Mutant female mice were slower to respond to heat.
Interactions
[edit]GIT2 has been shown to interact with GIT1.[14]
References
[edit]- ^ Premont RT, Claing A, Vitale N, Freeman JL, Pitcher JA, Patton WA, Moss J, Vaughan M, Lefkowitz RJ (Dec 1998). "beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein". Proc Natl Acad Sci U S A. 95 (24): 14082–7. doi:10.1073/pnas.95.24.14082. PMC 24330. PMID 9826657.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Premont RT, Claing A, Vitale N, Perry SJ, Lefkowitz RJ (Aug 2000). "The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing". J Biol Chem. 275 (29): 22373–80. doi:10.1074/jbc.275.29.22373. PMID 10896954.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ a b "Entrez Gene: GIT2 G protein-coupled receptor kinase interactor 2".
- ^ EUCOMM. "Git2Gt(XG510)Byg". www
.knockoutmouse .org. Retrieved 11 April 2011. {{cite web}}: External link in|publisher= - ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ^ a b Van der Weyden L, White JK, Adams, DA, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
- ^ a b c d Wellcome Trust Sanger Institute. "MGP Phenotyping of Git2Gt(XG510)Byg". Mouse Resources Portal. www
.sanger .ac .uk. Retrieved 11 April 2011. {{cite web}}: External link in|publisher= - ^ Wellcome Trust Sanger Institute. "Hot Plate Data for Git2". Mouse Resources Portal. www
.sanger .ac .uk. Retrieved 11 April 2011. {{cite web}}: External link in|publisher= - ^ Wellcome Trust Sanger Institute. "Plasma Chemistry Data for Git2". Mouse Resources Portal. www
.sanger .ac .uk. Retrieved 11 April 2011. {{cite web}}: External link in|publisher= - ^ Wellcome Trust Sanger Institute. "Haematology (CBC) Data for Git2". Mouse Resources Portal. www
.sanger .ac .uk. Retrieved 11 April 2011. {{cite web}}: External link in|publisher= - ^ Wellcome Trust Sanger Institute. "Homozygote Viability Data for Git2". Mouse Resources Portal. www
.sanger .ac .uk. Retrieved 11 April 2011. {{cite web}}: External link in|publisher= - ^ Wellcome Trust Sanger Institute. "Fertility Data for Git2". Mouse Resources Portal. www
.sanger .ac .uk. Retrieved 11 April 2011. {{cite web}}: External link in|publisher= - ^ Kim, Seho; Ko, Jaewon; Shin, Hyewon; Lee, Jae-Ran; Lim, Chunghun; Han, Jin-Hee; Altrock, Wilko D.; Garner, Craig C.; Gundelfinger, Eckart D.; Premont, Richard T.; Kaang, Bong-Kiun; Kim, Eunjoon (2003). "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo". J. Biol. Chem. 278 (8). United States: 6291–300. doi:10.1074/jbc.M212287200. ISSN 0021-9258. PMID 12473661.
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