The 22Q11.

2 deletion syndrome in
Zebrafish
22Q11.2 Deletion syndrome
(DiGeorge Syndrome)

• Prevalence 1 in 4000 newborns

• Deletion of 30-45 genes from

chromosome 22q11.2

• Common symptoms represented by

cardiac, cranio-facial and
neurodevelopmental abnormalities.

• Increased prevalence of neurological

disorders like schizophrenia
 Genes of interest

• 6 mitochondrial genes:
• SLC25A1
• ZDHHC8
• TXNRD2
• PRODH
• TANGO2
• MRPL40
 Function
Encodes mL40
Defects in this gene impair the
mitochondrial permeability transition pore
thus hindering it’s capacity to act as a Ca2+
buffer

Gene characteristics
MRPL40 Not duplicated
One splicing variation

Research Background
studies showed neurodevelopmental
abnormalities in C. elegans, fruit fly and
impaired WM in mice.
 MRPL40 structure
EXON 1 EXON 2 EXON 4
EXON 3
UTR UTR

5762 bp

Normal splicing

200 aa
UTR UTR

883 bp
 MRPL40 structure
EXON 1 EXON 2 EXON 4
EXON 3
UTR UTR

MO 5762 bp

MO induced splicing

UTR UTR

~805 bp
RT-PCR Primers
292 bp amplicon 612 bp amplicon

618 bp amplicon
MRPL40 cDNA
GATAACGGAAGTGTTTTTACACTGACCTACAGATCCACACTGGCCACTGAAAGGAGCAAAACATTTAATTTCTCACATTTTATGTTTGTAAAGTGGAT

ATTTCTGTAAATTATGGCGGGATTTGTGTGTCGTGCTGTAAACCGGATTATTTCGAGTCAATCCTCGTGTTGCAGTCCTGTTATTGCTGTCAGACACAG
AATCCTCGTGGTACGTATGTGACTT Intronic region
TCACTGGTTTACCTCAATGCTTTCGTTGAAAACTTCCGCACCATTAAGAGCCGAACCCAGGAAGAAGAAGAAGAAGGTGGACCCGCGGCAAGAAA

TTTTAGTGAAGGACCGACTGAAGAAGAGACTGAAAAGGATGGAGAAAGTCTCTCCAGAACTGATTCCCATTGAAGACTTCATAACTTCAGCCAAAA

GCTTCGACGACACCAGAACGCGTGCTCTTCCAGAAGTGTGTTTCGAGGAGAGCGAG
GCTTCGACGACACCAGAACGCGTGCTCTTCCAGAAGTGTGTTTCGAGGAGAGCGAGCGCAGAGCTCTGCTGCTGAAGGAATGGTCCAGACACAA

ACACAAACAGCACCAGATGGAGATGCAGGAGATCCAGGAGGCGCTGAAAGCCCAAAAGCAGGCGCTGATGCAGCTGAAACTGGAGTCTAAAGA

GCTTTACATTGCTGCGCTCCGTCCTGATACAGACACGCTGCCTTTCCTGCATCACGGGCCCAGTTACACTCCACCCATCGCTGACTATGAGGCTCCAG

AGGGAAAATATAATGACATTACACGTGTTTATACACAGTGAGGAGAGACGGTGACTGTATACAGGTGAAGAATAAAAATAATAAGTGTTCAATTAAG
AGGGAAAATATAATGACATTACACGTGTTTATACACAGTGAGGAGAGACGGTGAC

GTCTCGGAGAATAAAATGTATTGACGTCATTATATTGTTGTGAATTTATAATTATGTTGTTAAATCATCATGTTGTGATCGAGTTTAAAGGTTAAAATAAA

AAAATAAAAGAA
 100 bp L 100 bp L

B B 55.5 56.5 57 58 59 60 61 62 63 64 B

Results
 100 bp L
100 bp L 5% DMSO 10% DMSO

58 59
B PC

Results
qPCR Primers
100 bp amplicon 108 bp amplicon

124 bp amplicon
 MRPL40 cDNA
GATAACGGAAGTGTTTTTACACTGACCTACAGATCCACACTGGCCACTGAAAGGAGCAAAACATTTAATTTCTCACATTTTATGTTTGTAAAGT

GGATATTTCTGTAAATTATGGCGGGATTTGTGTGTCGTGCTGTAAACCGGATTATTTCGAGTCAATCCTCGTGTTGCAGTCCTGTTATTGCTGTC

AGACACAGTCACTGGTTTACCTCAATGCTTTCGTTGAAAACTTCCGCACCATTAAGAGCCGAACCCAGGAAGAAGAAGAAGAAGGTGGACC
AGACACAGTCACTGGTTTACCTCAATGCTTTCGTTGAAAACTTCCGCACCAT

CGCGGCAAGAAATTTTAGTGAAGGACCGACTGAAGAAGAGACTGAAAAGGATGGAGAAAGTCTCTCCAGAACTGATTCCCATTGAAGACTT

CATAACTTCAGCCAAAAGCTTCGACGACACCAGAACGCGTGCTCTTCCAGAAGTGTGTTTCGAGGAGAGCGAGCGCAGAGCTCTGCTGCTG
CATAACTTCAGCCAAAAGCTTCGACGACACCAG

AAGGAATGGTCCAGACACAAACACAAACAGCACCAGATGGAGATGCAGGAGATCCAGGAGGCGCTGAAAGCCCAAAAGCAGGCGCTGAT

GCAGCTGAAACTGGAGTCTAAAGAGCTTTACATTGCTGCGCTCCGTCCTGATACAGACACGCTGCCTTTCCTGCATCACGGGCCCAGTTACAC

TCCACCCATCGCTGACTATGAGGCTCCAGAGGGAAAATATAATGACATTACACGTGTTTATACACAGTGAGGAGAGACGGTGACTGTATACAG
TCCACCCATCGCTGACTATGAGGCTCCAGAGGGAAAATATAATGACATTACACGTGTTTATACACAGTGAGGAGAGACGGTGACTGTAT

GTGAAGAATAAAAATAATAAGTGTTCAATTAAGGTCTCGGAGAATAAAATGTATTGACGTCATTATATTGTTGTGAATTTATAATTATGTTGTTAA

ATCATCATGTTGTGATCGAGTTTAAAGGTTAAAATAAAAAAATAAAAGAA
 100 bp L

B PC

Results
Sample size for
Morpholino
injections
 NIC

3 ng/ul
Injection 6 ng/ul
Design
9 ng/ul

Control 9 ng/ul
 Head size

Eye size
Potential
Readouts
Hearth development

Synaptogenesis