Disease models Flashcards
frozen addicts- southern cali 1982
a 42 year old addict in a californian jail became paralysed. His symptoms caused by a bad batch of synthetic heroin, were indistinguishable from those associated with Parkinsons. Doctors traced his symptoms to an addictive he had ingested in a bad batch of heroin. How case helped unlock some mysteries about parkinson.
parkinsons disease
a degeneratie nerve disorder, related to loss of dopamine. Dopamine is predominately produced in the substantia nigra
- parkinsons is cause by specific loss of dopamine producing neutrons
symptoms of parkinson are relieved by
L-DOPO or levadopa
what causes the addicts to freeze
impurities found in bad batch of heroine called MPTP targeted a region of the midbrain called the substantia nigra. This area contains most of the cells which produce the NT, dopamine essential for control of movement and feeling pleasure
although humans are the only animals to get parkinson..
several therapies such as deep brain stimulation and different drugs were tested on animals
mice can be made diabetic with chemical
type 1 diabetes is caused by an autoimmune destruction of insulin producing B-cells
- chemical destruction go B-cells can used to induce hyperglycaemia
- test therapies to lower blood sugar
normal mice can also be used e.g.
to test the response t burns or infections
don’t always have to use whole animals e.g.
in the CML case unit we saw how individual cells could modified with BCR-ABL
- imatinib could be tested in vitro.
what is the difference between cells in a dish and in a body
- 2D vs 3D matrix
- cell/cell contact
- complex signal
- matrix rigidity
- pO2- normoxic conditions
mice
- mammals, small and fast breeding
- several inbred strains exist which mimic aspects of human disease.
- however do not necessarily reflect cause of human disease
why are inbred mice good to use
due to them having similar genetic background- can control environment
what makes a good disease model
- small
- cheap
- short lifespans
- easy to care for
- similar genes to humans
- breed quickly and have multiple offspring
Saccharomyces cerevisiae
Yeast Used for biological studies of cell processes (e.g., mitosis) and diseases (e.g., cancer)
Pisum sativum
Pea plant Used by Gregor Mendel to describe patterns of inheritance
Drosophila melanogaster
Fruit fly Employed in a wide variety of studies ranging from early gene mapping, via linkage and recombination studies, to large scale mutant screens to identify genes related to specific biological functions
Caenorhabditis elegans
Roundworm (nematode) Valuable for studying the development of simple nervous systems and the aging process
Danio rerio
Zebra fish Used for mapping and identifying genes involved in organ development
Mis musculus
House mouse Commonly used to study genetic principles and human disease
Rattus norvegicus
Brown rat Commonly used to study genetic principles and human disease
mutant mice
inbred
- make targets gene knock-outs ad knock ins
- informed by genetic research
how to make a mouse
- order or design and produce modified ES cells (embryonic stem cells)
- microinjection into fertilise oocytes in blastocyst stage
- transfer to pseudopregnant females
- birth of litter
- breed chimeric offspring with wild-type mice
- screen for germline transmission
- expansion
knockouts
performed to determine the physiological function of a gene- can model diseases- test treatments and reveal developmental roles
knockins
introduce specific mutations
SCID-NOD mouse
- no immune system
- allows tissue grafting
limitations of mutant mice
- which strain are you using
- what time of day do you do your experiments
- do men o women perform the experiments
- is your age clean
- mice and not humans
‘all models are..
bad- but some are useful’
the cystic fibrosis mouse
- CFTR gene clone in 1989
- 1990 mouse produced bit its fine
- need to use a knock out pig
in CF in humans/pigs
ATPase upregulated- achica conditions inhibit immun e clearance
- as well as Cl- channels being close
CF in mice
ATPase not unregulated
- cl- channels closed
CRISPR
- new gene editing tool
- quick, chip
- touted as a cure for hereditary and many other types of disease
CRISPR is used to create
knock-out/ knock-in cells and mice models
CRISPR is much more effective at knocking out genes than
designing your own embryonic stem cell
