NonHumanModel: Zhang_Mouse

GeneAlteration: Exon 2 of RAB39B was targeted using two gRNAs and Cas9 mRNA in the C57BL/6N background. Mice harboring 397-bp deletions in exon 2 were obtained.

ModelPhenotype: HP:0000256 Social and memory deficits

HumanPhenotype: HP:0001249, HP:0000256

ModelEvidence: Similar to PMID: 33364235, authors show through ASD-related tests that KO mice exhibit social and memory deficits. They also show that RAB39B variation results in over-proliferation and differentiation deficits of neural progenitor cells, which results in larger that normal number of neurons. Mice therefore have macrocephaly.

ModelVariant:

WhereInPaper:

The model is scored reduced points as the mice recapitulate the ASD phenotype seen in some human patients with RAB39B variants, but does not provide evidence for the Parkinson disease phenotype. (0.5)

NonHumanModel: Niu_Mouse

GeneAlteration: Transcription activator like effector nuclease (TALEN) - mediated strategy was used to target exon 1 of RAB39B to generate the knockout mice in the C57BL/6J background. A mouse line with a "GT" deletion at nucleotide 106-107 that caused a frameshift and early truncation of RAB39B was obtained. Authors confirmed absence of RAB39B loss of fucntion.

ModelPhenotype: Learning and memory deficits

HumanPhenotype: HP:0001249

ModelEvidence: 2-mo hemizygous male knock-out (KO) mice showed behavioral alterations compared to WT mice. KO mice showed reduced anxiety, impaired recognition memory, impaired short-term working memory, impaired spatial memory, impaired social novelty recognition, compromised motor skill learning, but motor ability was not affected. Authors indicate that impaired learning and memory was associated with altered synaptic plasticity.

ModelVariant:

WhereInPaper:

The evidence is scored minimal points as the phenotype recapitulated aligns with the human ID phenotype; however, the model provides no evidence of Parkinson disease phenotype. (0.5)