SHIRPA

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SHIRPA is a standardized set of experimental procedures used by scientists to characterize the phenotype of genetically modified laboratory mice. The protocols are designed to test muscle function, cerebellar function, sensory function and neuropsychiatric function. [1]

Contents

Origin

SHIRPA is an acronym of SmithKline Beecham, Harwell, Imperial College, Royal London Hospital, phenotype assessment), proposed in 1997 by a group of researchers from a number of British institutions and the pharmaceutical company, SmithKline Beecham. [2] [3] There are up to 40 tests in SHIRPA, across three screens of increasing complexity and specialization. [2] The first describes the behaviour of the mouse subject by observation. The second involves a more thorough behavioural assessment and includes pathological analysis. The third screening stage is focused on potential animal models of neurological disease. [3] [4]

Testing of mutant mice

The protocol has been used to test several mutant mice, [5] including dystrophin-deficient mutants, [6] transgenic models of amyotrophic lateral sclerosis [7] and Alzheimer's disease, [8] and a spontaneous mutant with degeneration of the cerebellum. [9]

Modifications

The first part of the SHIRPA protocol was changed to include observations on morphology and dysmorphology. This protocol became known as the "modified SHIRPA" and has been used to screen for dominant phenotypes in mice. [10]

See also

Related Research Articles

Molecular genetics Scientific study of genes at the molecular level

Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens. The field of study is based on the merging of several sub-fields in biology: classical Mendelian inheritance, cellular biology, molecular biology, biochemistry, and biotechnology. Researchers search for mutations in a gene or induce mutations in a gene to link a gene sequence to a specific phenotype. Molecular genetics is a powerful methodology for linking mutations to genetic conditions that may aid the search for treatments/cures for various genetics diseases.

Dystrophin Rod-shaped cytoplasmic protein

Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex (DAPC). Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere. It has a molecular weight of 427 kDa

Duchenne muscular dystrophy Type of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis followed by the arms. This can result in trouble standing up. Most are unable to walk by the age of 12. Affected muscles may look larger due to increased fat content. Scoliosis is also common. Some may have intellectual disability. Females with a single copy of the defective gene may show mild symptoms.

GLI2

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GLI3

Zinc finger protein GLI3 is a protein that in humans is encoded by the GLI3 gene.

Reeler

A reeler is a mouse mutant, so named because of its characteristic "reeling" gait. This is caused by the profound underdevelopment of the mouse's cerebellum, a segment of the brain responsible for locomotion. The mutation is autosomal and recessive, and prevents the typical cerebellar folia from forming.

Lamin B2

Lamin B2 is a protein that in humans is encoded by the LMNB2 gene. It is the second of two type B nuclear lamins, and it is associated with laminopathies.

MYO7A

Myosin VIIA is protein that in humans is encoded by the MYO7A gene. Myosin VIIA is a member of the unconventional myosin superfamily of proteins. Myosins are actin binding molecular motors that use the enzymatic conversion of ATP - ADP + inorganic phosphate (Pi) to provide the energy for movement.

CHD7

Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene.

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Genetically modified mouse

A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or as animal models of human diseases, and are also used for research on genes. Together with patient-derived xenografts (PDXs), GEMMs are the most common in vivo models in cancer research. Both approaches are considered complementary and may be used to recapitulate different aspects of disease. GEMMs are also of great interest for drug development, as they facilitate target validation and the study of response, resistance, toxicity and pharmacodynamics.

Scrambler is a spontaneous mouse mutant lacking a functional DAB1 gene, resulting in a phenotype resembling that seen in the reeler mouse. The strain was first described by Sweet et al. in 1996.

Jacqueline Crawley Behavioral neuroscientist

Jacqueline N. Crawley is an American behavioral neuroscientist and an expert on rodent behavioral analysis. Since July 2012, she is the Robert E. Chason Chair in Translational Research in the MIND Institute and professor of psychiatry and behavioral sciences at the University of California, Davis School of Medicine in Sacramento. Previously, from 1983–2012, she was chief of the Laboratory of Behavioral Neuroscience in the intramural program of the National Institute of Mental Health. Her translational research program focuses on testing hypotheses about the genetic causes of autism spectrum disorders and discovering treatments for the diagnostic symptoms of autism, using mouse models. She has published more than 275 peer-reviewed articles in scientific journals and 110 review articles and book chapters. According to Scopus, her works have been cited over 36,000 times, giving her an h-index of 99. She has co-edited 4 books and is the author of What's Wrong With my Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice, which was very well received.

GRXCR1

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ZZZ3

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International Mouse Phenotyping Consortium

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The Mouse Genetics Project (MGP) is a large-scale mutant mouse production and phenotyping programme aimed at identifying new model organisms of disease.

Stephen D. M. Brown

Steve David Macleod Brown is director of the Medical Research Council (MRC) Mammalian Genetics Unit, MRC Harwell at Harwell Science and Innovation Campus, Oxfordshire, a research centre on mouse genetics. In addition, he leads the Genetics and Pathobiology of Deafness research group.

AGTPBP1 (gene)

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References

  1. ↑ Hatcher JP, Jones DN, Rogers DC, et al. (November 2001). "Development of SHIRPA to characterise the phenotype of gene-targeted mice". Behav. Brain Res. 125 (1–2): 43–7. doi:10.1016/s0166-4328(01)00275-3. PMID   11682092. S2CID   6313756.
  2. 1 2 Nolan PM, Peters J, Strivens M, et al. (August 2000). "A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse". Nat. Genet. 25 (4): 440–3. doi:10.1038/78140. PMID   10932191. S2CID   9028853.
  3. 1 2 Rogers, D. C.; Fisher, E. M. C.; Brown, S. D. M.; Peters, J.; Hunter, A. J.; Martin, J. E. (1997). "Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment". Mammalian Genome. 8 (10): 711–713. doi:10.1007/s003359900551. PMID   9321461. S2CID   29864514.
  4. ↑ Rogers DC, Peters J, Martin JE, et al. (June 2001). "SHIRPA, a protocol for behavioral assessment: validation for longitudinal study of neurological dysfunction in mice". Neurosci. Lett. 306 (1–2): 89–92. doi:10.1016/S0304-3940(01)01885-7. PMID   11403965. S2CID   44756347.
  5. ↑ Lalonde R, Strazielle C (May 2021). "SHIRPA as a neurological screening battery in mice". Current Protocols. 1 (5): 482–488. doi:10.1002/cpz1.135. PMID   4000103. S2CID   234770535.
  6. ↑ Rafael JA, Nitta Y, Peters J, Davies KE (September 2000). "Testing of SHIRPA, a mouse phenotypic assessment protocol, on Dmd(mdx) and Dmd(mdx3cv) dystrophin-deficient mice". Mamm. Genome. 11 (9): 725–8. doi:10.1007/s003350010149. PMID   10967129. S2CID   12996210.
  7. ↑ Lalonde R, Eyer J, Wunderle V, Strazielle C (May 2003). "Characterization of NFH-LacZ transgenic mice with the SHIRPA primary screening battery and tests of motor coordination, exploratory activity, and spatial learning". Behav Proc. 63 (1): 9–19. doi:10.1016/S0376-6357(03)00013-5. PMID   12763264. S2CID   2508969.
  8. ↑ Lalonde R, Dumont M, Staufenbiel M, Strazielle C (February 2005). "Neurobehavioral characterization of APP23 transgenic mice with the SHIRPA primary screen". Behav. Brain Res. 157 (1): 91–8. doi:10.1016/j.bbr.2004.06.020. PMID   15617775. S2CID   35239762.
  9. ↑ Jacquelin C, Strazielle C, Lalonde R (September 2011). "Neurologic function during developmental and adult stages in Dab1(scm) (scrambler) mutant mice". Behav. Brain Res. 226 (1): 265–273. doi:10.1016/j.bbr.2011.09.020. PMID   21945093. S2CID   140205214.
  10. ↑ Masuya H, Inoue M, Wada Y, et al. (November 2005). "Implementation of the modified-SHIRPA protocol for screening of dominant phenotypes in a large-scale ENU mutagenesis program". Mamm. Genome. 16 (11): 829–37. doi:10.1007/s00335-005-2430-8. PMID   16284798. S2CID   35870158.
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