Table 2 Phenotype of available knockout/knockdown models for highly conserved 22q11.2 deletion region genes (n = 17)

PRODH

−

No (KO)

Not assessed (KO, prodha); − (LOC100537991)

No (KO)

Reduced accumulation rate of newly synthesized proteins, extended life span, increased thermo-tolerance (KD)

Hyperprolinemia, locomotor defects including indecisive movement patterns and hypoactivity (KO); Not assessed (KD)

Not assessed (KO, prodha); − (LOC100537991)

Reduced male body weight and prepulse inhibition (genetic background dependent), impaired fear conditioning, regionally altered levels of proline (hyperprolinemia), glutamate, gamma-aminobutyric acid, and aspartate in the brain (KO)

DGCR14

Embryonic lethality (KO); No (het-KO)

−

−

Not assessed (KO)

Higher frequency of male progeny, meiotic prophase defect (KD); Deregulated mRNA processing (KO); Normal phenotype (het-KO)

Not assessed (KD)

−

Not assessed (KO)

SLC25A1

−

Embryonic lethality (KO)

− (slc25a1a, slc25a1b)

Majority die before 12 weeks post-natal (KO)

Normal when assessed for lethality, sterility, anatomical morphology, development, and growth (KD)

Chromosomal breaks and global loss of DNA acetylation (KO)

Mitochondrial depletion, flattened head, small heart, brain, inner ear, intestine, and mandibular arch skeleton with defect severity proportional to gene suppression, neuromuscular junction defects regardless of phenotype severity (KD, slc25a1a); Not assessed (slc25a1b)

Mice examined at two weeks are small and sickly, and show generalized hypoplasia, most severely in liver and bone marrow (KO)

HIRA

Embryonic lethality (KO)

Embryonic lethality (KO)

−

Embryonic lethality (KO); No (het-KO)

Not assessed (KO, KD)

Enhanced transcriptional suppression through variegation with transposable element probe, offspring of null mothers crossed with wild-type males do not develop while paternal null offspring show only partial lethality implying maternal effect (KO); Not assessed (KD)

Not assessed (KD)

Disrupted gastrulation, abnormal cardiac development (e.g., heart chambers), abnormal embryonic tissue morphology, abnormal placenta, craniofacial abnormalities, failure of brain to fuse and abnormal neural plate morphology (KO); Decreased leukocyte cell count (het-KO)

MRPL40

−

Embryonic lethality (KO)

−

Not assessed (KO)

Slow growth, larval arrest, reduced brood size, sterile progeny (KD)

Gross neuroanatomical defects due to under-proliferation of neuroblast cells during neurogenesis (KO); Not assessed (KD)

−

Not assessed (KO)

UFD1L

−

No (KO)

Embryonic lethality (KO)

Not assessed (KO); No (het-KO)

Slow growth, gonad development deficits, enlarged gut granules, locomotor defect with deviations in self-propelled movement, patchy coloration, reduced life span (KD)

Stress response reduced as determined by virus infection assay (KO); Not assessed (KD)

Decreased eye size, abnormal head shape due to hypoplasia and misarranged features, necrotic central nervous system, increased thickness of mandibular arch skeleton, hypoplastic gut and liver (KO)

Not assessed (KO); Viable with no obvious heart defects (het-KO)

CDC45

Embryonic lethality (KO)

Lethal in the larval stage (KO)

Not assessed (KO)

Embryonic lethality (KO); No (het-KO)

Everted vulva, reduced brood size, sterility associated with no sperm development (KO); Sister chromatid segregation defective in early embryo, reduced brood size (KD)

Gross neuroanatomy defective due to reduced cellular proliferation causing small neuroblast size in the developing brain (KO); Not assessed (KD)

Not assessed (KO)

Impaired proliferation of inner cell mass after embryo implantation (KO); Normal when assessed for size, behaviour, and sterility (het-KO)

Gene^a

C. elegans

D. melanogaster

D. rerio

M. musculus

C. elegans

D. melanogaster

D. rerio

M. musculus

TBX1

No (KO)

Partial embryonic lethality (KO)

Embryonic lethality (KO)

Embryonic lethality (KO); No (het-KO)

Abnormal uterine cell fate due to transcriptional abnormalities (KO); Normal when assessed for sterility, anatomical morphology, and development (KD)

Severely malformed or absent adult muscle precursors and supportive alary heart muscles (KO); Not assessed (KD)

Severely abnormal cardiac development (e.g., absent aortic arch), severe pouch defects and abnormal facial skeletal development, abnormal inner ear morphology (KO); Severely abnormal cardiac development (e.g., absent aortic arches) and thymus (KD)

Severely abnormal cardiac development (e.g., aortic arch), abnormal inner, middle, and outer ear morphology, abnormal lymphangiogenesis, abnormal cranial base morphology (KO); Mild cardiac abnormalities (e.g., fourth aortic arch arteries) and decreased prepulse inhibition (het-KO)

TXNRD2

–

–

–

Embryonic lethality (KO)

Hypersensitive to protein aggregation induced paralysis (KD) but otherwise normal when assessed for morphology and development (KO, KD)

Not assessed (KD)

–

Severe anemia and growth retardation due to perturbed cardiac development and augmented apoptosis of hematopoietic cells (KO)

TANGO2

–

Not assessed (KO)

Not assessed (KO)

–

Not assessed (KD)

Not assessed (KO, KD)

–

–

DGCR8

No (KO)

Lethal before end of pupal stage (KO)

Not assessed (KO)

Embryonic lethality (KO); No (het-KO)

Accumulation of miRNA target protein, decreased lifespan (KO); Reduced miRNA processing, accumulation of target mRNA, vulva defects, enhanced locomotor deficits of unc mutant (uncoordinated) phenotypes (KD)

Abnormal olfactory projection and mushroom body neuron morphology and neurophysiology (KO); Not assessed (KD)

Not assessed (KO)

Reduced dendritic spine number, reduced dendritic complexity, decreased prepulse inhibition and abnormal spatial working memory (het-KO)

TRMT2A

No (KD)

No (KO)

Not assessed (KO)

Not assessed (KO)

Not maternally sterile but otherwise not assessed (KD)

Not sterile (KO); Not assessed (KD)

Not assessed (KO)

Not assessed (KO)

MED15

Reduced lifespan (KO)

Pupal lethality (KO)

–

–

Sterile, small, increased apoptosis, decreased protein expression, changes in mRNA expression, intestinal morphology, reduced lifespan, uncoordinated locomotion (KD); Hypersensitivity to toxin exposure (KO, KD)

Abnormal wing development (KO, het-KO); Abnormal wing development and shortened legs, formation of ectopic sensory organs and induced cellular apoptosis (KD)

Disruption of dorsal/ventral patterning and mesoderm development (KD)

–

PI4KA

Embryonic lethality (KO)

Lethal before end of larval stage (KO)

–

Embryonic lethality (KO)

Slow growth and sterility (KD)

Abnormal eye morphology, neuromuscular junction overgrowth (KO); Not assessed (KD)

Decreased eye, head, and mesenchymal cell proliferation, increased apoptosis and necrosis of brain cells (KD)

Premature death due to degeneration of mucosal cells in the stomach and intestines (KO)

SNAP29

Embryonic lethality (KO)

Pupal lethality (KO)

–

Pre-weaning lethality (KO)

Defects in secretion from intestinal epithelial cells (KO); Sterility associated with endomitotic oocytes and pre-mitotic maturation of the oocyte, abnormal localization of phospholipid membrane components (KD)

Not assessed (KO); Synaptic defects characterized by abnormal basal neurotransmission. Lethality observed in the pupal stage (KD)

Disrupted pigmentation, epidermal irregular spatial pattern, disorganized keratinocyte cell surface (KD)

Not assessed (KO)

AIFM3

–

No (KO)

–

–

Normal when assessed for lifespan and sterility, anatomical morphology, development, and growth (KD)

Not sterile (KO); Not assessed (KD)

–

–

SLC7A4

–

Not assessed (KO)

Not assessed (KO)

–

Normal when assessed for sterility and anatomical morphology (KD)

Not assessed (KO, KD)

Not assessed (KO)

–